OBJECTIVE Evaluate responses and safety of ritonavir-boosted atazanavir ("boosted atazanavir") compared to unboosted atazanavir among antiretroviral-naïve patients in the clinical managed care setting. METHODS Observational cohort analysis of atazanavir use (comparing ritonavir-boosted to non-boosted) at Kaiser Permanente and Group Health Cooperative from 2003 to 2006. Antiretroviral-naïve patients initiating atazanavir were followed through 52 weeks of treatment. RESULTS 443 patients were prescribed atazanavir (69 non-boosted; 15.5%). Boosted and non-boosted atazanavir groups were similar with respect to gender and age. Boosted atazanavir use was associated with greater odds achieving HIV RNA <400 c/mL (odds ratio [OR] = 3.24, p = .008), greater decrease in HIV RNA (-0.37 log10/mL, p = .03), greater increase in CD4 T-cell count (+59 cells/microL, p = .01), and greater increase in total bilirubin (+1.21 mg/dL as opposed to +0.56 mg/dL, p .001). There were no statistically significant differences for glucose, liver transaminases, total cholesterol, or LDL cholesterol elevations. There were greater odds of maximal viral control when atazanavir was combined with tenofovir or zidovudine in combination with lamivudine (or emtricitabine). CONCLUSIONS Ritonavir-boosted atazanavir is associated with greater virologic control and immune response through 52 weeks compared to non-boosted atazanavir, without greater risk of adverse events except elevated bilirubin. Thus, ritonavir-boosted atazanavir is the preferred method of prescribing atazanavir.