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To obtain data on the evolution of carotid lesions, we evaluated 133 patients at their first antiretroviral regimen, followed for at least 2 years; 77 treated with protease inhibitors (PIs): Group A and 56 with non-nucleosidic reverse transcriptase inhibitors (NNRTIs): Group B. All patients were subjected to carotid ultrasonography. In Group A, among the previously normal patients 22.5% developed lesions, 40% remained normal, 37.5% shifted to other antiretroviral regimens. Among the 37 previously pathologic patients, 46% worsened, 19% were stable, in 8% the lesions had disappeared, 27% shifted. In Group B, among the previously normal patients, 12.7% developed lesions, 80.8% remained unaltered, 6.5% shifted. Among the previously pathologic patients, 12.5% worsened, lesions reversed in 25%, remained stable in 50% and 12.5% shifted to PI. At statistical analysis, in Group A both the percentage of patients developing new lesions and the percentage of patients who worsened was significantly higher. In conclusion, we evidenced a more rapid onset of lesions in patients treated with PIs with respect to patients treated with NNRTIs and towards a more rapid evolution of the previous lesions. The shift from PIs to NNRTI/3 NRTI seems related to a lower rate of evolution. Interestingly, a disappearance of lesions was detected in both groups.