Background: Previous studies showed a significant prognostic value of 3-year and 5-year evolution of noninvasive fibrosis tests in European chronic hepatitis C (CHC) patients with or without HIV. It is uncertain whether this conclusion can be extrapolated to Chinese patients and whether the assessment of noninvasive fibrosis tests in a shorter time interval still has a prognostic value. Objectives: The study aimed to assess the prognostic value of changes of aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis-4 (FIB-4) in consecutive years in Chinese CHC patients. Methods: There were 173 CHC patients enrolled in 2 centers in this retrospective study. APRI and FIB-4 were calculated every 12 /- 2 months. The average difference between 2 adjacent calculations was defined as an annual change (AC). Risk factors were evaluated by Cox proportional regression models. Results: Cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver-related death developed in 29 patients during the median follow-up of 47.0 (29.5 - 72.0) months. Baseline FIB-4 and APRI, Child-Pugh class C, non-sustained virologic response (SVR) to interferon (IFN) or Pegylated IFN plus ribavirin, and AC of FIB-4 were significantly associated with liver disease progression. AC of FIB-4 (P< 0.001) exhibited a more robust prognostic value than AC of APRI (P = 0.228). Excellent prognosis was observed in patients with AC of FIB-4 3.25 and AC of FIB-4 > 0.22, or non-SVR and AC of FIB-4 > 0.22 had the highest cumulative incidence of liver disease progression among the 4 groups identified according to baseline FIB-4 and AC of FIB-4, or SVR and AC of FIB-4. Conclusions: An increased FIB-4 over time is an independent risk factor of liver disease development in Chinese CHC patients. Monitoring FIB-4 annually may help physicians to predict prognosis in CHC patients.