The aim of this study was to describe the natural history of HCV after 16 years of infection, in a cohort of individuals who acquired their infections on a known date in the United Kingdom. A total of 924 HCV-infected transfusion recipients (cases) and 475 anti-HCV negative transfusion recipients (controls) were eligible for inclusion in the study. Survival was compared between cases and controls to see if there was any excess mortality attributable to HCV. The results show that all-cause mortality was not significantly different between cases and controls (hazard ratio 1.17, 95% CI 0.92-1.49, P=0.21). However, the risk of death directly from liver disease was higher in cases than controls (hazard ratio 2.71, 95% CI 1.09-6.75, P=0.03). Nearly 30% of those HCV-infected cases who died directly from liver disease were known to have consumed excess alcohol.