Estimates of hepatitis C virus (HCV) clearance following acute infection range from 14 to 46%. This wide range is likely to be due to the characteristics of the populations studied and analysis methods. This paper examines how differing definitions of clearance parameters affect estimates of viral clearance in a cohort of 85 injecting drug users with newly acquired HCV infection. Kaplan-Meier estimates of time to HCV clearance were determined using varying definitions of eligible cohort, viral clearance, date of infection and date of clearance. Based on which combinations of definitions were used, the number of subjects eligible for analysis ranged from 27 to 75, clearance rate ranged from 14 to 68% and time to achieving 25% clearance ranged from approximately 5 months to 14 months. Standardized definitions and methodologies are required to enable valid comparisons of rates of clearance across newly acquired HCV infection natural history studies.