Background and AimChinese herbal medicine (CHM), as well as Western medicine (WM), is an important cause of drug-induced liver injury (DILI). However, the differences between CHM and WM as agents implicated in liver injury have rarely been reported. MethodsOverall, 1985 (2.05%) DILI cases were retrospectively collected from the 96857 patients hospitalized because of liver dysfunction in the 302 Military Hospital between January 2009 and January 2014. ResultsIn all the enrolled patients with DILI, CHM was implicated in 563 cases (28.4%), while 870 cases (43.8%) were caused by WM and the remaining patients (27.8%) by the combination of WM and CHM. Polygonum multiflorum was the major implicated CHM. Compared with WM, the cases caused by CHM showed more female (51 vs 71%, P<0.001) and positive rechallenge (6.1 vs 8.9%, P=0.046), a much greater proportion of hepatocellular injury (62.2 vs 88.5%, P<0.001), and a higher mortality (2.8 vs 4.8%, P=0.042); however, no differences in the rates of chronic DILI and ALF were found (12.9 vs 12.4%, P=0.807; 7.6 vs 7.6%, P=0.971). Based on Roussel Uclaf Causality Assessment Method, 75.6% of cases caused by CHM were classified as probable and only 16.6% as highly probable, significantly different from WM (38.4 and 60.3%, all P<0.001). ConclusionsThe causal relationship between CHM and liver injury is much complex, and the clinical characteristics of DILI caused by CHM differ from those caused by WM.