OBJECTIVES: To estimate the incidences of hospitalizations for statin-related adverse events (AEs) and further evaluate the influence of the concomitant use of fibrates or cytochrome P450 (CYP) 3A4 inhibitors on the risks of AEs in patients initiating statin treatments. METHODS: A retrospective cohort study design was employed with analyses from the Taiwan National Health Insurance Research Database between January 1, 2000 and December 31, 2007. The study cohort comprised patients initially treated with statins, and was followed to observe the occurrence of hospitalizations for statin-associated AEs, including myopathy, renal adverse events, hepatotoxic events and acute pancreatitis. Use of statins was further categorized into three groups to examine the effect of concomitant use of the interacting drugs: statin-fibrate combination, statin-CYP3A4 inhibitor combination, and statin monotherapy. Poisson regressions were used to estimate the individual incidences and incidence rate ratios (IRRs) of hospitalization events for the combined therapies versus statin monotherapy. RESULTS: A total of 53,594 statin initiators were identified as the study cohort, with atorvastatin and lovastatin being observed as the most commonly prescribed statins. The proportion of statin initiators concomitantly treated with fibrates and CYP3A4 inhibitors was 7.1% and 14.3%, respectively. Overall, the highest incidence occurred in renal adverse events (36.8/10,000 person-years), followed by hepatotoxic events, acute pancreatitis, and myopathy. A similar ranking order of the incidences was observed across the three groups. Compared to statin monotherapy, combination therapy of statins with the interacting medications increased the risks of overall AEs (statin-fibrate combination: adjusted IRR, 2.01; 95% CI, 1.21-3.32; statin-CYP3A4 inhibitor combination: adjusted IRR, 2.29; 95% CI, 1.73-3.02). CONCLUSIONS: Renal toxicity is found to be the most frequently occurring AE during statin treatments. Concomitant use of statins with fibrates or CYP3A4 inhibitors increases the risks of statin-associated AEs, which warrants caution for close monitoring of adverse symptoms when statins are used concurrently with the potential interacting drugs.