Objective: In POWER 1 and POWER 2, Darunavir (TMC114) with low-dose Ritonavir (Darunavir/r) demonstrated greater efficacy versus control protease inhibitors (PIs). To examine the efficacy and safety of the selected Darunavir/r dose further, additional patients were analyzed. Methods: Treatment-experienced HIV-1–infected patients received Darunavir/r at a dose of 600/100 mg twice daily plus an optimized background regimen. The primary intent-to-treat analysis was the proportion of patients with an HIV-1 RNA reduction $1 log10 at week 24. Results: Three hundred twenty-seven patients were treated; the baseline mean HIV-1 RNA was 4.6 log10 copies/mL, and the median CD4 count was 115 cells/mm3 (median primary PI mutations = 3, PI resistance-associated mutations = 9). Two hundred forty-six patients reached week 24 by the cutoff date and were included in the efficacy analysis: 65% and 40% achieved HIV-1 RNA reductions of $1 log10 and, 50 copies/mL, respectively, at week 24. The mean CD4 count increase was 80 cells/mm3. The most common adverse events (AEs) were diarrhea (14%), nasopharyngitis (11%), and nausea (10%). Nine (3%) patients discontinued treatment because of AEs or HIV-1–related events. Six treatment-unrelated deaths (2%) were reported. Conclusions: These results corroborate POWER 1 and POWER 2. In this larger set of treatment-experienced patients, Darunavir/r at a dose of 600/100 mg twice daily provided substantial virologic and immunologic responses and was generally safe and well tolerated.