Objective To assess the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) for the prevention of colorectal neoplasia. Methods A systematic review of all relevant randomized controlled trials and quasi-randomized controlled trials of NSAIDs for prevention of colorectal neoplasms was performed by using The Cochrane Collaboration recommended methods. Results Nine trials were included and assessed. There was sufficient evidence for aspirin to prevent the development of colorectal adenomas compared with placebo in three trials of high quality and large sample size with relative risk (RR) 0.81, 95% confidence interval (CI) 0.72 to 0.91 and P=0.000 5 . No adequate evidence supported aspirin in the prevention of development of colorectal cancer (RR 0.97, 95% CI 0.79 to 1.20, P= 0.79). However, there was no evidence to support sulindac and celecoxib curing or preventing colorectal adenomas or familial adenomatous polyposis (RR 0.71, 95% CI 0.49 to 1.03, P= 0.07 and RR 0.90, 95% CI 0.76 to 1.07, P=0.23). No evidence on the dose of NSAIDs was used for prevention of colorectal adenomas at present. No significant difference was seen in the number of adverse events between patients taking NSAIDs and those taking placebo (P=0.9). Conclusions Aspirin may prevent the development of colorectal adenomas and may avoid polypectomy for 1 in every 10 to 18 persons but we don’t know whether aspirin can be substituted for endoscopically removed colorectal polyps. However, the true clinical benefit for prevention of colorectal neoplasia of NSAIDs should be considered.