This study aimed to evaluate the outcomes of chronic hepatitis B patients with cirrhosis who received long-term nucleos(t)ide analog therapy. A total of 546 consecutive cirrhotic patients treated with entecavir (n=359), telbivudine (n=104), or tenofovir (n=83) for chronic hepatitis B were enrolled. The incidence of hepatocellular carcinoma (HCC) and overall survival were evaluated. During a median follow-up of 39months, 56 (10.3%) patients developed HCC and 14 (2.6%) patients died. These outcomes were not associated with different antiviral use. Cox proportional hazard analysis showed that old age (≥60years) [hazard ratio (HR), 1.74; p=0.046], statin use (HR, 2.42; p=0.017), low platelet count (<100,000/μL; HR, 2.00; p=0.039), and variceal bleeding history (HR, 5.12; p<0.001) were independent factors for HCC development. With regard to survival, Child-Pugh B/C (HR, 3.78; p=0.039) and low platelet count (<105/μL; HR, 7.82; p=0.049) were independent factors. The estimated glomerular filtration rate significantly increased in patients receiving telbivudine (p=0.047), but decreased in those receiving tenofovir (p<0.001) at Year 2. Tenofovir use (HR, 1.98; p=0.005) was one of the independent factors associated with the progression of chronic kidney disease stage. Long-term nucleos(t)ide analog therapy does not guarantee against the HCC development and mortality in chronic hepatitis B-related cirrhotic patients. Careful HCC surveillance is necessary in patients with old age, statin use, low platelet count, and variceal bleeding history.