Adenomatous polyps are known precursor lesions for colorectal cancer and some hyperplastic polyps also have malignant potential. The use of aspirin and nonsteroidal anti-inflammatory drugs (NSAID) is associated with a reduced risk of adenomatous polyps; however, less evidence exists with regard to NSAID use and hyperplastic polyp risk. We conducted a colonoscopy-based case-control study including 2,028 polyp cases (1,529 adenomatous and 499 hyperplastic) and 3,431 polyp-free controls. Multivariate logistic regression models were constructed to derived adjusted ORs and 95% CIs as the measure of the association between NSAID use and polyp risk. Use of baby aspirin, regular aspirin, and nonaspirin NSAIDs, were associated with a reduced risk of adenomatous polyps (OR = 0.79, 95% CI: 0.66-0.93, OR = 0.73, 95% CI: 0.58-0.90, and OR = 0.67, 95% CI: 0.53-0.86, respectively). Baby aspirin was also associated with a reduced risk of hyperplastic polyps (OR = 0.74, 0.56-0.97). Although a dose response was seen with adenoma risk and regular use of any NSAIDs (less than 7 doses per week, 7 doses per week, and greater than 7 doses per week), a dose response was not seen with hyperplastic polyps. We found no evidence of interaction between NSAID dose and duration and polyp risk. The use of any NSAID regardless of type was associated with a reduced risk of adenomatous polyps; however, regular aspirin and COX-2 inhibitors use was not associated with hyperplastic polyp risk.