Inclusion Criteria:

• Known diagnosis of histologically-confirmed BE with or without dysplasia (as defined by the presence of specialized columnar epithelium anywhere in the tubular esophagus with ≥ 1 cm of circumferential involvement or non-circumferential involvement of specialized columnar epithelium that is ≥ 2 cm in length) requiring radiofrequency ablation
• Documentation of complete ablation of BE after radiofrequency ablation on two endoscopic examinations at least 3 months apart (including no evidence of Barrett's esophagus on surveillance biopsies) as determined by the pathologist at each site; completion of ablation should have occurred no greater than 24 months prior to randomization
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this trial, she should inform the research personnel and her clinical care provider immediately
• Willingness to provide tissue samples for research purposes
• No chronic use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors during the 3 months prior to randomization; chronic use is defined as any aspirin or NSAID use on ≥ 7 days during the 3 months preceding the beginning of randomization
• Hemoglobin ≥ 10 g/dL or hematocrit ≥ 30%
• Leukocyte count ≥ 3,000/microliter
• Platelet count ≥ 100,000/microliter
• Absolute neutrophil count ≥ 1,500/microliter
• Creatinine ≤ 2.5 x institutional upper limit of normal (ULN)
• Or glomerular filtration rate (GFR) > 30 ml/min/1.73 m^2
• Total bilirubin ≤ 2 x institutional ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 2.5 x institutional ULN
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN
• A negative serum pregnancy test done ≤ 7 days prior to pre-registration, for women of childbearing potential only
• Eastern Cooperative Oncology Group (ECOG) performance status &te; 2
• Ability to understand and the willingness to sign a written informed consent document; a legally authorized representative (LAR) may sign informed consent for persons who do not have the capacity to legally consent to take part in the study

Exclusion Criteria:

• Inability to abstain from, NSAID (including aspirin), and selective COX-2 inhibitor therapy at the time of randomization through the completion of the study (the study period is defined as baseline to exit endoscopy at 18 months after randomization which defines the completion of the study); participants may take Tylenol and non-NSAID pain relievers
• Current or planned use of anticoagulant drugs such as: warfarin, heparin, low molecular weight heparin, Plavix, or Aggrenox throughout the course of the study

• Individuals taking the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 3 months prior to starting aspirin or placebo on this study; consultation with the participant's primary care provider will be obtained prior to stopping any agent; the use of the following drugs or drug classes is prohibited during aspirin/placebo treatment:

  • NSAIDs: such as aspirin, Naprosyn, ketorolac and others NSAIDs
  • COX-2 inhibitors: such as celecoxib, rofecoxib
  • Valproic acid
  • Sulfinpyrazone
  • Probenecid
  • Corticosteroids (other than short-term use defined as less than 2 weeks)
  • Platelet aggregation inhibitors, except in a monitored antithrombotic regimen
  • Methotrexate (MTX)
  • Vaccines containing live viruses
  • Gingko
• Individuals with uncontrolled renal insufficiency or renal failure
• Participants with prior fundoplication, bariatric surgery or any other major upper gastrointestinal (GI) surgery; cholecystectomy will not be grounds for exclusion
• History of cancer diagnosis ≤ 24 months prior to randomization, excepting non-melanoma skin cancer or carcinoma-in-situ of the cervix
• History of cancer treatment ≤ 12 months prior to randomization, excepting hormonal therapy (except treatment for non-melanoma skin cancer or carcinoma-in-situ of the cervix)
• Receipt of any other investigational agents ≤ 3 months prior to randomization, except innocuous agents with no known interaction with the study agents (e.g., standard dose multivitamins or topical agents for limited skin conditions), at the discretion of the Protocol Lead Investigator at each participating site
• History of allergic reactions attributed to aspirin or compounds of similar chemical or biologic composition to the study agent
• History of endoscopically or radiographically diagnosed peptic ulcer disease with upper GI bleeding during the past 5 years or history of endoscopically or radiographically diagnosed peptic ulcer disease with upper GI bleeding any time while taking aspirin
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, bleeding disorder, vitamin K deficiency, alcohol abuse (defined as ingestion of 3 or more drinks per day) or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women
• Breast feeding women
• Surveillance biopsies demonstrating residual BE at qualifying exam
• Presence of an esophageal stricture defined as "any recognizable change in esophageal luminal caliber that is accompanied by symptoms of dysphagia, or any asymptomatic narrowing that either will not allow any adult endoscope to pass or allows passage with resistance"
• Patients with human immunodeficiency virus (HIV) infection