Inclusion Criteria:

* History of Stage 0-III colon or rectal cancer with primary resection 1 year previously
* Post-operative colonoscopy and CT scans of chest, abdomen \& pelvis showing no evidence of disease
* Must not have cardiovascular risk factors including unstable angina, history of myocardial infarction, or cerebrovascular accident, coronary artery bypass surgery, or NY Heart Assoc Class III or IV heart failure.
* Patients must not have known uncontrolled hyperlipidemia (defined as LDL-C \>/= 190 mg/dL or triglycerides \>/= 500 mg/dL within the past 3 years or uncontrolled high blood pressure (systolic blood pressure \> 150 mm Hg) within 28 days prior to registration
* At least 30 days from completion of adjuvant chemo and RT.
* Presence of gastroesophageal reflux disease acceptable if controlled with medications
* Not receiving or planning to receive concomitant intravenous corticosteroids on a regular basis,nonsteroidal anti-inflammatory drugs (NSAIDs), nor anticoagulants on a regular predictable intermittent basis. NSAID use must not exceed 10 days per month; Maximum aspirin dose

* 100 mg per day or ≤ two 325 mg tablets per week. Inhaled steroids (i.e. for asthma or related conditions) are allowed.
* Able to swallow oral medications
* Laboratory: WBC ≥ 4.0 x 1000/mcL, platelets ≥ 100,000/mcL and hemoglobin \> 11.0 g/dL. (A total WBC ≥ 3.1 x 1000/mcL is allowed for non-Hispanic black males and total WBC ≥ 3.4 x 1000/mcL for non-Hispanic black females. Serum bilirubin ≤ 2.0 mg/dL and AST (SGOT) or ALT(SGPT) ≤ 2 x IULN. Serum creatinine ≤ 1.5 x IULN
* Zubrod PS 0-1, 18 years of age or older
* Will not participate in any other clinical trial for the treatment or prevention of cancer unless off protocol treatment, on follow-up phase only
* Offered opportunity to participate in blood specimen banking

Exclusion Criteria:

* History of colon resection \> 40 cm
* Mid-low rectal cancer
* Recurrent or metastatic disease
* High cardiovascular risk; Uncontrolled hypertension
* Planned radiation therapy or additional chemotherapy
* Documented history of gastric/duodenal ulcer within last 12 months and/or current treatment or active symptoms of gastric/duodenal ulcer
* Known history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease
* ≥ 30 dB uncorrectable hearing loss for age of any of the five tested frequencies on prestudy audiogram
* Known hypersensitivity to sulindac or excipient byproducts. Previous asthma, urticaria, or allergic-type reaction to aspirin or other NSAIDs
* Significant medical or psychiatric condition that would preclude study completion (8 years)
* No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for \> 5 years
* Pregnant or nursing women. Women/men of reproductive potential must agree to use effective contraception