This study tested gender-based differences in performance of students in science, engineering, technology, and math (STEM) Information Systems (IS) courses. Data collected from 94 STEM-designated information systems courses (STEM-IS) courses and 2,189 students over a 9-year period were analyzed using ANOVA. This study tested for differences in performances for all the subclassifications and combinations of the sample such as gender-based differences by course type (technical vs. conceptual) and by course level (graduate vs. undergraduate). The results indicate that female students in STEM-IS courses performed better overall, as well as in all the sub-classifications by course type, undergraduate and graduate course levels, and technical and conceptual course types than the male students. The statistical analysis was followed up with a post hoc analysis of structured interviews of faculty and students in STEM-IS courses to corroborate the results obtained from ANOVA. The importance and implications of the results are discussed.