Recent research has drawn attention to protective effects of statins on colorectal cancer (CRC) and possible joint effects with other drugs. Because statins are often administered in combination with low-dose aspirin for the prevention of cardiovascular disease, the aim of our study was to investigate individual and combined effects of statins and low-dose aspirin on CRC risk. We assessed use of statins and low-dose aspirin in 540 cases with histologically confirmed incident CRC and 614 control subjects in a population-based case–control study in Germany. Multiple logistic regression was used to estimate the impact of regular use of either low-dose aspirin or statins, and of both drugs combined on CRC risk. We found modest risk reduction of CRC for regular use of low-dose aspirin (adjusted odds ratio 0.77, 95% confidence interval 0.55–1.07) and a stronger association with regular use of statins (OR 0.65, 95% CI 0.43–0.99) or use of both drugs (OR 0.63, 95% CI 0.36–1.10). Combined use of low-dose aspirin and statins was associated with risk reduction by 62% after 5 or more years (OR 0.38, 95% CI 0.15–0.97). Combinational chemoprevention with low-dose aspirin and statins might provide stronger risk reduction than either of the single drugs after at least 5 years use, but confirmation is needed, preferably in prospective cohort studies and eventually by randomized controlled trials. © 2007 Wiley-Liss, Inc.