OBJECTIVES: Simvastatin is an antihyperlipidemic agent used to lower serum cholesterol. Simvastatin has been associated with rhabdomyolysis, a rare but potentially life-threatening Adverse Drug Event (ADE).  Recently, the FDA created a black box warning limiting use of simvastatin at higher doses. The objective of this study was to evaluate the data in the FDA Adverse Event Reporting System (FAERS) to describe and profile the cases that led to this decision. METHODS: A retrospective analysis of all domestic and foreign reports of simvastatin-associated rhabdomyolysis between October 1997 and September 2011 was conducted using FAERS database. The frequency of the following outcomes was examined: congenital anomaly, death, life-threatening reaction, hospitalization, disability, others and required intervention. The percentage of role codes (primary suspect, secondary suspect, concomitant drug, or interacting drug) was analyzed. Separate analysis was conducted to report frequency of doses associated with rhabdomyolysis. Drug dosages associated with both ADEs and specifically rhabdomyolysis were evaluated. RESULTS: A total of 3,014,229 simvastatin-associated reports were identified over a 14-year period in the FAERS database. Hospitalization occurred in 41.1% and death was reported in 8.16% of the cases. Remarkably, 40.4% of ADE were reported for the 40mg dose and 13.4% for the 80mg dose. Simvastatin was designated as concomitant in 73.6% and as a secondary suspect in 16.0% of the cases.  A total of 25,701 reports of simvastatin-associated rhabdomyolysis were reported. Of these, 6,673 rhabdomyolysis reports had dose information avaialble. Whereas, 44.1% were associated with the 40 mg dose; 26.7% were reported for 80mg dose. CONCLUSIONS: Simvastatin-associated ADE were demonstrated in the FAERS database with severe clinical outcomes including hospitalization and death. The increased risk associated with higher simvastatin doses provides evidence to support the FDA’s black box warning.