To characterize survival and to compare rates of disease progression to death of human immunodeficiency virus (HIV)-infected patients, between those initiating multiple-drug rescue therapy (MDRT) and those antiretroviral-inexperienced initiating triple-drug antiretroviral therapy (ART), we conducted a population-based analysis of HIV-infected men and women aged > or =18 years in British Columbia, Canada. Cumulative mortality rates were estimated by use of Kaplan-Meier methods, and Cox-proportional hazard regression was used to model the simultaneous effect of prognostic variables on survival. Cumulative mortality at 36 months was 14.2%+/-2.0% and 10.9%+/-1.0% for the MDRT and triple-drug ART groups, respectively (P=.105, log-rank test). After adjustment for other baseline prognostic variables, MDRT was found not to be a predictor of increased all-cause mortality (relative risk, 1.17; 95% confidence interval, 0.82-1.66) in multivariate analysis. Over the short-term, patients receiving MDRT had relatively low mortality. After adjustment for baseline prognostic factors, rates of survival were comparable with those in patients initiating triple-drug ART.