A new teaching format, the LecturePlus, was formulated as a lecture followed by small-group learning activities. This study assessed the effectiveness of LecturePlus in medical education. An interventional study was conducted among final-year medical students, with 74 students in the experimental group and 96 students in the control group. Each LecturePlus lasted [tilde]1 h and was conducted with 12-18 students. A LecturePlus session comprised of a lecture followed by small-group problem-solving exercises. The exercises were clinical cases with open-ended short-answer questions. Students were divided into groups of three (triads) for these exercises. A faculty tutor assisted the small groups as needed. Closure was achieved through a discussion moderated by the tutor. Learning outcomes were assessed via the National Board of Medical Examiners (NBME) subject scores and compared with those of the preceding academic year. An additional multiple-choice question (MCQ) test was administered before and after the clerkship. The MCQ test showed improvement in knowledge application (P < 0.001, partial eta squared = 0.42). There was a statistically significant improvement in adjusted NBME scores among female students (74.8 vs. 71.8; P = 0.017) but not among male students. An anonymous written questionnaire survey showed high ratings for LecturePlus (95% selecting yes or partly yes to overall satisfaction). LecturePlus is an instructional strategy that integrates a lecture with learning activities. It can be scaled to large class sizes facilitated by one teacher. By combining didactic teaching with problem-solving, this new instructional strategy may foster application of knowledge.