Aim: To compare computer-assisted self-interview (CASI) with routine face-to-face interview (FTFI) for sexual history taking from patients in a clinical setting. Methods: A randomised controlled trial was undertaken at the Melbourne Sexual Health Centre, Melbourne, Victoria, Australia, in 2005. New, walk-in patients triaged into the centre were eligible for the study. Those who consented to the study were randomly allocated (initially at a ratio of 2:1, then 1:1) to either CASI or FTFI. Those randomised to CASI also subsequently undertook FTFI. Results: During the study period, of 713 patients approached, 611 agreed to participate in the study; 356 were randomised to FTFI and 255 to CASI. Overall, the responses to questioning using CASI and FTFI were similar except that women undertaking the CASI reported a significantly higher median number of male partners for the preceding 12 months (3 v 2, p = 0.05) and the CASI participants reported previous hepatitis B vaccination more often (50% v 37%, p = 0.01). Most participants found the CASI either easy (31; 13%) or very easy (193; 82%) to complete; 83 (35%) were comfortable and 121 (51%) were very comfortable with it. Conclusions: CASI may be a reliable, efficient and highly acceptable method for the screening of sexual risk in clinical sexual health settings and could be used routinely to improve the efficiency of clinical services.