Since pre-internship medical students appeared inefficient in acquiring fundamental knowledge in large classes, a hybrid instructional method of problem-and-lecture-based learning (PLBL) was designed to leverage the complementary strengths of PBL in reasoning under minimal guidance and LBL in immediate knowledge retention. We improved PBL (IPBL) in its instructional process and grading in a way that's feasible in large classes, divided in IPBL almost 50 students into 7-10 squads as a figure simulating student counts in classic PBL class to strive for each squad member to achieve the same level of knowledge, and applied IPBL to about half of the instructional contents while LBL to another half for their complementary strengths. In this case, PLBL led to more number of test questions correctly answered by all students in a class, more students in higher test score buckets, and higher student perception scores on the methodology. PLBL facilitates fundamental knowledge acquisition in large classes within 50 students prior to medical internships.