Undergraduate attrition from science, technology, engineering, and mathematics is well documented and generally intensifies during intermediate years of college. Many contributing factors exist; however, a mismatch between timing of certain pedagogical approaches, such as case-based learning, and the level of students' cognitive abilities plays a crucial role. Using cognitive load theory as a foundation, we examined relationships between case-based learning versus a traditional lecture and learning gains of undergraduates within an intermediate physiology course. We hypothesized instruction via a case study would provide greater learning benefits over a traditional lecture, with gains possibly tempered by student characteristics like academic preparation, as measured by ACT scores, and academic age, as measured by credit hours completed. Results were surprising. Case-based learning did not guarantee improved learning gains compared with a traditional lecture for all equally. Students with lower ACT scores or fewer credit hours completed had lower learning gains with a case study compared with a traditional lecture. As suggested by cognitive load theory, the amount of extraneous load potentially presented by case-based learning might overwhelm the cognitive abilities of inexperienced students.