Although adherence to HAART at a level above 95% has been associated with optimal viral suppression, the impact of different levels of adherence on long-term clinical outcomes has not been determined. We used an objective pharmacy-based measure to examine the association between three levels of adherence to HAART and disease progression among a population-based cohort of HIV-infected patients attending an urban HIV specialty clinic. Higher levels of adherence to HAART were significantly associated with longer time to virologic failure (P < 0.001), greater increase in CD4 cell count (P = 0.04), and lower risk of progression to clinical AIDS or death (P < 0.007). After controlling for other factors, patients with low adherence had over five times the risk of disease progression than patients with moderate adherence (P = 0.007) or patients with high adherence (P = 0.001). There was no significant difference in the risk of progression between patients with moderate and high levels of adherence (P > 0.2). Patients who progressed to AIDS or death had significantly higher viral loads (P = 0.01) and lower CD4 cell counts (P = 0.03) than patients who experienced virologic failure, but did not progress.