Inclusion Criteria:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Has a history of ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) completed at least 1 year prior to the Day 1 (Randomization) Visit.
• Has pouchitis that is chronic or recurrent, defined by an modified pouchitis disease activity index (mPDAI) score ≥5 assessed as average from 3 days immediately prior to the Baseline endoscopy and a minimum endoscopic subscore of 2 (outside the staple or suture line) with either (a) ≥3 recurrent episodes within 1 year prior to the Screening Period treated with ≥ 2 weeks of antibiotic or other prescription therapy, or (b) requiring maintenance antibiotic therapy taken continuously for ≥4 weeks immediately prior to the Baseline Endoscopy Visit.
• Agrees to take ciprofloxacin (500 mg twice daily) on Day 1 and through Week 4, regardless of the previous treatment and to stop any previous antibiotic therapy on Day 1 of the study (additional courses of antibiotics will be allowed, as needed, for flares after Week 14.)
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use a barrier method of contraception (e.g., condom with spermicide) from signing of informed consent throughout the duration of the study and for 18 weeks after last dose. The female partner of a male subject should also be advised to use a highly effective method of contraception
• A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use a highly effective method of contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.

Exclusion Criteria - Gastrointestinal Exclusion Criteria:

• Has Crohn's disease (CD), or CD of the pouch.
• Has irritable pouch syndrome (IPS).
• Has isolated or predominant cuffitis.
• Has mechanical complications of the pouch (eg, pouch stricture or pouch fistula).
• Currently requires or has a planned surgical intervention for UC during the study.
• Has diverting stoma.

Exclusion Criteria - Infectious Disease:

• Has evidence of an active infection (e.g., sepsis, cytomegalovirus, or listeriosis) during Screening.
• Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:
  • A diagnostic TB test performed within 30 days of Screening or during the Screening Period that is positive, as defined by:
  • A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests; OR
  • A tuberculin skin test reaction ≥ 10 mm (≥ 5 mm in participants receiving the equivalent of > 15 mg/day prednisone); OR
  • Chest X-ray within 3 months prior to Day 1 that is suspicious for pulmonary TB, and a positive or 2 successive indeterminate QuantiFERON test within 30 days prior to Screening or during the Screening Period.
• If participant is HCV antibody positive, then a viral load test will be performed. If the viral load test is positive then the participant will be excluded.
• Has evidence of active infection with C difficile during Screening (to be confirmed by laboratory test).
• Has any prior exposure to vedolizumab, natalizumab, efalizumab, rituximab, etrolizumab, or anti- mucosal addressin cell adhesion molecule-1 (MAdCAM-1) therapy.
• Has a history of hypersensitivity or allergies to vedolizumab or its components.
• Has allergies to and/or contraindications for ciprofloxacin, a history of tendon disorders related to quinolone administration and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency. Further conditions requiring precautions for use of ciprofloxacin have to be considered based on local prescribing information.
• Is taking, has taken, or is required to take any excluded medications.
• Has received any investigational or approved biologic or biosimilar agent within 60 days prior to Randomization.
• Has received an investigational nonbiologic therapy within 30 days prior to Randomization.
• Has received an approved nonbiologic therapy (including 5-aminosalicylate [5-ASA], corticosteroid, azathioprine, 6-mercaptopurine [6-MP], etc.) in an investigational protocol within 30 days prior to Randomization.
• Has received any live vaccinations within 30 days prior to randomization.
• Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist at Screening.
• Has had a kidney, heart, or lung transplant.
• Has a history of malignancy, except for the following: adequately-treated non-metastatic basal cell skin cancer; squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to the Screening visit; and history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to Screening. Participants with a remote history of malignancy (e.g., >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to enrollment.
• Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating, or neurode-generative disease.
• Has conditions, which in the opinion of the investigator, may interfere with the participant's ability to comply with the study procedures.
• Has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal (GI), genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety.
• Has any of the following laboratory abnormalities during the Screening Period:

Hemoglobin level < 8 g/dL.

• White blood cell (WBC) count < 3 × 10^9/L;
• Lymphocyte count < 0.5 × 10^9/L;
• Platelet count <100 × 10^9/L or > 1200 × 10^9/L;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × the upper limit of normal (ULN);
• Alkaline phosphatase > 3 × ULN;
• Serum creatinine > 2 × ULN.
• Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection** or a known history of human immunodeficiency virus (HIV) infection (or is found to be seropositive at Screening) or subject is immunodeficient (e.g., due to organ transplantation, history of common variable immunodeficiency, etc.).

* Participants who are positive for hepatitis B virus surface antigen (HBsAg) will be excluded. For participants who are negative for HBsAg but are positive for either surface antibodies and/or core antibodies, HBV DNA polymerase chain reaction will be performed and if any test result meets or exceeds detection sensitivity, the participant will be excluded.

General Exclusion Criteria:

• If female, the participant is pregnant or lactating or intending to become pregnant or nurse before, during, or within 18 weeks after the last dose of study medication; or intending to donate ova during such time period.
• If male, the participant intends to donate sperm or father a child during the course of this study or for 18 weeks after the last dose of study medication.
• Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to Screening.