Numerous experimental, epidemiological and clinical trails have suggested non-steroidal anti-inflammatory drug(NSAID) usage potentially reduces the risk of developing cancers. Since NSAIDs are relatively inexpensive, NSAIDs may offer a possible strategy to reduce the burden of cancer. However, before NSAIDs canbe considered as chemopreventives, their potential benefit must be weighed against the risks of their adverse events. We purposed to establish the risk-benefit profile of NSAIDs as chemopreventives against solid tumor cancers i.e.digestive, lung, breast, gynecologic, prostate and urinary tract cancers. We sought to determine any association between NSAID usage and incident cancers, as well as NSAID-related gastrointestinal(GI) and renal adverse events. Two separate retrospective cohort studies were conducted using Georgia(GA) and North Carolina(NC) Medicaid claims. Medicaid recipients aged 50-100 who had at least 2 years continuous eligibility were analyzed. We excluded subjects, who had any diagnoses of cancer, GI, or renal diseases within their first year of eligibility. Cohorts members were followed until the earliest occurrence of:(1)outcomes of interest:cancers, GI events(i.e.GI ulcers and hemorrhage) and renal events(e.g.renal failure),(2)loss of eligibility,(3)death, or (4)end of study (December 31,2001 for GA cohort; December 31,1998 for NC cohort). All outcome occurrences were determined by searching for claims with indicative ICD-9-CM codes. NSAID exposure was identified by searching the National Drug Code in the prescription files. For each NSAID prescription, the strength and prescribed quantifies were kept to further explore a dose-response relationship. Survival Analysis was used to calculate all relative risks. The significant chemopreventive benefit of NSAIDs was established against colorectal, esophageal, lung, prostate, and endometrial cancer. Besides no correlation between incidence rate of pancreatic cancer and NSAID usage, any NSAID exposure was possibly associated with the risk reduction in breast, lung, gastric, liver, gynecologic and urinary tract cancers. There was no increased risk of GI or renal adverse effects with NSAID prescribing in this population. The dose-response relationship between NSAID use and incident cancer, as well as their adverse events was delineated. The higher the cumulative exposure, the lower the incident cancer and NSAID adverse event risks. Further research is needed since questions about optimal chemopreventive dose schedule of NSAIDs are unanswered.