Low dose-ritonavir boosted protease inhibitors are increasingly being used for the first-line antiretroviral treatment, though their virological efficacy has just poorly been compared to alternative antiretroviral therapies. Here, we retrospectively investigated the virological responses of 316 protease inhibitor-naive HIV patients receiving highly active antiretroviral treatment based on a single (n = 256) or a ritonavir-boosted protease inhibitor (n = 60), both in the background of two nucleoside analogues. - By intent-to-treat analysis, a complete initial virological response was achieved in 71.8% of all patients in the single protease inhibitor group (indinavir: 76%, ritonavir: 67.5%, nelfinavir: 70.6%) and in 88.3% (p = 0.008) of patients treated with a boosted protease inhibitor (saquinavir/r: 71.4%, indinavir/r: 92.1%, lopinavir/r: 86.6%). The multivariate risk analysis identified boosted PI treatment as an independent predictor of a complete virological response (OR = 2.8, p=0.02). Viral rebound after an initial complete virological response was observed in 28% and 17% (p = 0.06) of patients receiving a single or a dual protease inhibitor, respectively. The rate of durable viral suppression over 12 months was 44.5% and 56.7% (p = 0.09) in the respective study cohorts. Ritonavir-boosted protease inhibitors therefore seem to induce a superior virological response rate and a higher degree of sustained virological suppression.