Case-based learning (CBL) has been proposed as an effective method to promote student knowledge and motivation. The timing and methods for implementation have varied among schools, and data regarding the effectiveness of this pedagogy compared to other learning modalities are inconclusive. We introduced five different cases in the first course of our medical school as part of small-group CBL, and monitored student satisfaction and performance in summative evaluations. We observed that (1) students were very satisfied with the CBL sessions; (2) performance in essay examinations was significantly higher in CBL topics, compared to non-CBL topics, as evaluated at the end of the course, and three months after course conclusion; and (3) there was a trend of higher performance in multiple-choice questions about CBL topics, but this was not statistically significant. Our results indicate that CBL is an acceptable pedagogy to be incorporated from the beginning of undergraduate medical education to promote acquisition and retention of knowledge, students' interest in foundational sciences, and integration of basic science disciplines and clinical medicine. When evaluating knowledge acquired using the CBL method, integrative essays represent a valuable tool to assess the depth of comprehension and application of information.