Purpose: The objective of this study was to determine the effect of a multi-modal curricular intervention designed to teach sexual history-taking skills to medical students. The Association of Professors of Gynecology and Obstetrics, the National Board of Medical Examiners, and others, have identified sexual history-taking as a learning objective for medical students. Methods: Between 2001 and 2003 the sexual history-taking skills of two sequential cohorts of second-year medical students were compared. Cohort I (n = 95) received a traditional physical diagnosis curriculum. Cohort II (n = 99) received the same curriculum in addition to a multi-modal sexual history-taking module. Both groups were evaluated at one year as part of a general clinical skills evaluation involving three standardized patient cases. The apparent relevance of the sexual history varied per case. Results: In the obvious-relevance case, nearly every student in Cohort II initiated a sexual history, performing significantly better than Cohort I (98% versus 86%, p less than 0.05). A significant positive association was found between the curricular intervention and the number of screening sexual history questions asked (odds ratio, 2.8; 95% confidence interval, 1.3-6.0). In the case with least-obvious relevance, no student in either cohort initiated a sex history. Conclusion: Under conditions of a general clinical skills evaluation, the intervention significantly improved second-year medical students' sexual history-taking skills in a case of obvious relevance but had less impact in cases where the relevance of the sex history was less obvious. (Contains 1 table and 1 figure.)