Process-oriented guided-inquiry learning (POGIL), a pedagogical technique initially developed for college chemistry courses, has been implemented for 2 yr in a freshman-level anatomy and physiology course at a small private college. The course is populated with students with backgrounds ranging from no previous college-level science to junior and senior biology, biochemistry, and forensic science majors. Fifty percent of the lectures in the course were replaced with POGIL activities, performed in class by students working collaboratively in small groups. The introduction of POGIL pedagogy into the second half of a two-semester anatomy and physiology course significantly improved student performance on summative evaluations. Overall course scores increased from a mean score of 76% to 89% in the three semesters after POGIL was introduced. Performance on the same multiple-choice final exam rose from a mean of 68% to 88% over the same time period. Most significantly, the rate of students earning a D or F in the course was halved in the first two semesters after POGIL was introduced and was 0% in the third semester. Student satisfaction with the method was high, and most students perceived the value of this form of instruction.