The first pilot vaccination program against hepatitis B in Peru was implemented in the hyperendemic Abancay province in 1991. To assess the impact of vaccination on mortality rates of hepatitis B-related hepatocellular carcinoma (HCC), cirrhosis, and fulminant hepatitis, we compared mortality trends before (1960–1990) and after (1991–2012) roll-out of the vaccination program, using death certificate data from the Municipalidad Provincial de Abancay. Our results showed that, following program roll-out, the overall mortality rates (per 100,000 population) decreased from 9.20 to 3.30 for HCC (95% CI, 1.28–10.48%; P < 0.014), from 16.0 to 6.3 for cirrhosis (95% CI, 3.20–16.10%; P < 0.004), and from 34.80 to 1.28 for fulminant hepatitis (95% CI, 16.70–50.30%; P < 0.001). The absolute number of deaths attributable to cirrhosis (10 [8.80%] vs. 0.0%; P < 0.001) and fulminant hepatitis (83 [40.0%] vs. 5 [19.20%]; P < 0.026) decreased in 5–14-year-old children following vaccination. These findings showed reduced mortality rates of hepatitis B-related liver diseases, particularly cirrhosis and fulminant hepatitis in children under 15 years, following implementation of the vaccination program against hepatitis B.