The Classroom Performance System (CPS) is an instructional technology that increases student performance and promotes active learning. This study assessed the effect of the CPS on student participation, attendance, and achievement in multicultural college-level anatomy and physiology classes, where students' first spoken language is not English. Quantitative method and quasi-experimental design were employed and comparative statistic methods and pre-post tests were used to collect the data. Participants were college students and sections of study were selected by convenience sampling. Participation was 100% during most of the lectures held while it did not strike above 68% in the control group. Attendance was significantly higher in CPS sections than the control group as shown by paired- samples t-tests. Experimental sections had a higher increase in the pre-post test scores and student averages on lecture exams increased at a higher rate than those of the control group. Therefore, the CPS increased student participation, attendance, and achievement in multicultural anatomy and physiology classes. The CPS can be studied in other settings where the first spoken language is English or in other programs, such as special education programs. Additionally, other variables can be studied and other methodologies can be employed.