Background Now there are no efficient prophylactic or treatment strategies for hepatic veno-occlusive disease (VOD). Therefore, it is critical to early identify patients at high risk of VOD. Aim To analyze the risk factors of VOD in the hematopoietic stem cell transplantation (HSCT) patients. Methods A comprehensive search of the population was conducted. Results Twenty-one studies with 27 679 HSCT patients were eligible. The incidence of VOD was 15% [95% confidence interval (CI) 13-17%]. The following were the risk factors for VOD: mismatched HLA [odds ratio (OR) 2.34, 95% CI 1.20-4.57, P = 0.01], history of liver disease (OR 2.72, 95% CI 2.03-3.64, P < 0.00001), elevated AST before transplant (OR 2.49, 95% CI 1.49-4.15, P = 0.0005), months from diagnosis to HSCT > 12 months (OR 1.76, 95% CI 1.15-2.69, P = 0.009), previous radiation (OR 1.86, 95% CI 1.49-2.31, P < 0.00001), busulphan (OR 3.69, 95% CI 2.58-5.29, P < 0.00001) and MTX (OR 1.81, 95% CI 1.22-2.69, P = 0.003). There were no significant differences for VOD presentation in the patients with regards to sex, number of HSCT, Karnofsky score <90%, unrelated donor, autologous HSCT, CYA and heparin prophylaxis. Conclusion Mismatched HLA, liver disease (history of liver disease, elevated AST), months from diagnosis to HSCT >12 months, previous radiation and use of hepatotoxic drugs (BU and MTX) are the independent risk factors for VOD in the HSCT patients.