The aim of this revision is to evaluate ethnicity and gender rate of enrolment in registrative clinical trials of the protease inhibitors (Pls) from 1996 to 2009. Company-sponsored, phase II or III registrative clinical trials of PIs were evaluated. Forty-nine clinical trials were included. Clinical trials were conducted in centres in North America (n = 39), Central-South America (n = 22), Europe (n = 22), Africa (n = 8), Asia (n = 5), Australia (n = 10). Overall mean age was 39.6 years; median proportion of women was 16.3%. The most represented ethnic group was Caucasian. A test for trend over time (1996-2009) shows a significant increase in the proportion of women included (P = 0.012), and a decrease in the proportion of Caucasians included, reaching borderline significance (P = 0.061). An inverse correlation was observed between the proportion of Caucasians and that of women enrolled in each study (r = -0.65, P < 0.0001). Women were less likely to be included in double-blind studies (11.2% versus 17%, P = 0.019). Clinical trials for treatment-naive subjects were more likely to enrol ethnicities other than Caucasian compared with Caucasian (44.7% versus 27.1%, respectively, P = 0.04). Rates of enrolment of minorities in registrative clinical trials for Pls show a positive trend since 1996, mirroring the growing number of people of different ethnic groups accessing ART.