Introduction: Liver involvement is common in hematological malignancies, but the incidence and pattern of liver injury vary among the different types. The aims of our study were to determine the incidence and clinical course of acute hepatitis and the important factors for its development in patients with leukemia after chemotherapy. Materials and methods: All patients with the diagnosis of leukemia who were treated at the Department of Hematology between January 2008 and January 2013 were included in the study. A detailed medical history, clinical and laboratory findings, treatment modalities, complications, and clinical course were recorded retrospectively. Results: A total of 124 patients (64 females) with the diagnosis of leukemia were included in the study. The mean age was 45.2 years (16–89 years) and mean follow-up time was 29.7 months (0.25–192 months). A total of 43 (34.6%) patients had acute hepatitis after chemotherapy. Pattern of liver injury was hepatocellular in 31 patients, cholestasis in 2, and mix in 10 patients. Age (p = 0.001), hepatitis B surface antigen (HBsAg, p = 0.007), acute leukemia (p < 0.001), positive blood culture (p = 0.004), the amount of transfused red blood cell (p = 0.001), and amount of transfused platelets (p = 0.002) were significantly different under univariate analysis between the acute hepatitis group and the nonacute hepatitis group. Under multivariate analysis, only acute lymphoblastic leukemia (ALL) was identified as independent predictive factor for development of acute hepatitis after starting chemotherapy. Conclusion: Acute and self-limited hepatitis develops in the substantial proportion of patients with leukemia. The most important factor for development of acute hepatitis is the type of leukemia.