Rationale, aims and objectives: Chronic hepatitis B virus (HBV) infection and alcoholism are the leading cirrhotic etiologies. Cirrhosis cases caused by different etiologies have different clinical features, which leads to different clinical outcomes. This study aimed to investigate the differences in complications between HBV- and alcohol-related cirrhosis. Methods: Medical records of hospitalized patients with HBV- or alcohol-related cirrhosis treated from January 2014 to January 2021 were retrospectively reviewed. The unadjusted rate and adjusted risk of cirrhotic complications between the two groups were assessed. Results: The rates of hepatocellular carcinoma (HCC) and hypersplenism were notably higher in HBV-related cirrhosis (HCC: 39.55% vs 1.45%, P < 0.001; hypersplenism: 45.84% vs 28.99%, P = 0.009), whereas the rates of hepatic encephalopathy (HE) and acute-on-chronic liver failure (ACLF) were higher in alcohol-related cirrhosis (HE: 15.94% vs 4.49%, P = 0.001; ALCF: 7.25% vs 2.28%, P = 0.040). After adjusting for potential confounders, HBV-related cirrhotic patients still had higher risks of HCC (odds ratio [OR] = 34.06, 95% confidence interval [CI]: 4.61–251.77, P = 0.001) and hypersplenism (OR = 2.29, 95% CI: 1.18–4.42, P = 0.014), while alcohol-related cirrhotic patients still had higher risks of HE (OR= 0.22, 95% CI: 0.06–0.73, P = 0.013) and ACLF (OR = 0.30, 95% CI: 0.14–0.73, P = 0.020). Conclusion: HBV-related cirrhotic patients had increased risks of HCC and hypersplenism, while alcohol-related cirrhotic patients more readily developed HE and ACLF.