Students’ course performance is fundamental for any institution to carry out its academic mission. Often, in-class disengagement and lack of after-class course support in large-enrollment classes trigger academic problems for students. This leads to poor exam performance and an increased rate of final letter grade of a D or F or student withdrawal (DFW), an indicator of students’ poor academic success. Changing teaching strategies by using interventions that incorporate student-student interaction and student-faculty interaction may offer the opportunity to improve course performance. In this retrospective study, we examined the effect of changing teaching strategies on student course performance of 5,553 students enrolled in an undergraduate health sciences course over a span of 20 semesters. Three different interventions namely 1) daily low-stake in-class quizzes, 2) team-based learning, and 3) after-class review sessions were incorporated as teaching strategies. To assess the combined effect of these strategies’ students’ performance in the intervention period (12 semesters) was compared with control period (8 semesters). Student performance in the course was measured by exam grades; overall score; percentage of students receiving letter grades and A, B, C; and DFW rates. The data indicated that in the intervention period, exam scores increased by 6.6%, overall course score increased by 6.2%, percentage of students receiving letter grade A/B increased by 21.3%, percentage of students receiving letter grade C decreased by 6.9%, and the DFW rates decreased by 14.5%. Overall, changing teaching strategies through incorporation of these interventions improved students’ performance in the course.