Adherence to treatment for hepatitis C virus (HCV) maximizes treatment efficacy. Missed doses and failing to persist on treatment are two patient-level processes that are rarely defined or analyzed separately from other factors affecting treatment adherence. We evaluated the prevalence and patterns of missed doses and nonpersistence, and identified patient characteristics associated with these outcomes. Missed doses of ribavirin (RBV) and peginterferon (PEG), measured prospectively in Virahep-C using electronic monitoring technology, were analyzed using generalized estimating equations. Cox proportional hazards models analyzed time to nonpersistence from baseline to week 24 (N=401) and from week 24–48 in Responders (N=242). Average proportion of PEG and RBV missed doses increased over time from 5 to 15% and 7 to 27%, respectively. Patients who were younger, African American, unemployed, or unmarried were at greater risk of missing PEG from week 0–24; higher baseline depression predicted missing PEG from weeks 24–48. Patients who were younger or African American were more likely to miss daily RBV from weeks 0–24; and those without private insurance or employment were more likely to miss RBV from weeks 24–48. Fifty-two patients failed to persist on treatment for patient-driven deviations. Predictors of nonpersistence from weeks 0–24 included younger age, lower education, public or no insurance, or worse baseline headaches. In conclusion electronic monitoring and the prospective Virahep-C design afforded a unique opportunity to evaluate missing doses and nonpersistence separately, and identify patients at risk for nonadherence. These processes will be important to investigate as the dosing schedules of antiviral regimens become increasingly complex