OBJECTIVES: Idiosyncratic drug induced liver injury (DILI) is a rare but potentially serious liver disorder and a major cause of significant liver injury. Limited data exist on racial differences in DILI incidence, presentation, and course. METHODS: We compared the causative agents, clinical features, and outcomes of DILI among self-described African-Americans and non-Hispanic whites (Caucasians) enrolled in the DILIN Prospective Study. Individuals with definite, highly likely, or probable DILI enrolled between September 2004 and February 2016 were included in this analysis. RESULTS: 144 African-Americans and 841 Caucasian patients met the eligibility criteria. Causal medications varied by race: trimethoprim/sulfamethoxazole being the most common cause among African-Americans (7.6 vs. 3.6%) followed by methyldopa (4 vs. <1%), phenytoin (5 vs. <1%), isoniazid (4 vs. 4%), and amoxicillin/clavulanate (4.1 vs. 13.4%). The severity of illness, however, tended to be greater in African-Americans than Caucasians as determined by peak mean bilirubin (14.3 vs. 12.8 mg/dl), INR (1.9 vs. 1.6), and DILIN severity score (3.0 vs. 2.6). The frequency of severe cutaneous reactions was significantly higher in African-Americans (2.1 vs. 0.36% in Caucasians, P=0.048). African-Americans also had higher rates of hospitalization (76.7 vs. 57.6%, P<0.001), liver transplantation or liver related death by 6 months (10.2 vs. 5.8%, P=0.02 after controlling for selected covariates), and chronic DILI (24 vs. 16%, P=0.06). CONCLUSIONS: The most common DILI causative agents differ between African-Americans and Caucasians. African-Americans are more likely to have severe cutaneous reactions and more severe liver injury leading to worse outcomes, including death and liver transplant.