Purpose: The purpose of this study is to assess the effects of case type and gender of standardized patient on student performance in a clinical performance examination (CPX). Methods: During 2005, an eight-station CPX was administered to fourth-year students from 4 medical schools. A total of 306 students, of which 206 (67%) were male, participated in the exam. Station checklists, scored by the SPs, consisted of history taking (Hx), physical examination (PE), information sharing (IS), clinical courtesy (CC) and patient-physician interaction (PPI). A measurement of students’ perceived difficulty was obtained through student questionnaires. The difference of CPX scores between male and female students were studied using Mann-Whitney s U. Results: Across the gender-neutral cases, female students scored better in Hx in 2 cases. In PE, IS and CC, the only difference seen was with CC in 1 case (female students scored higher). In PPI, female students performed better than male students in all female SP cases and one male SP case, but, there was a significant student gender-SP gender interaction when averaging all cases. For the gender sensitive case, there was no significant difference in all checklist categories in the male case when student gender was considered. In the female case, female students performed better than male students only in PPI. Student questionnaires revealed that there was no significant difference in perceived difficulty between male and female students. Conclusion: The standardized patients ratings in gender sensitive cases are not affected by the gender of standardized patients and students, except in PPI with a female case where female students performed better than male students.