Our study compared the performance of students enrolled in a graduate-level introductory biostatistics course in an online versus a traditional in-person learning environment at a school of public health in the United States. We extracted data for students enrolled in the course online and in person from 2013 to 2018. We compared average quiz and final exam scores between students in the two learning environments adjusting for demographic characteristics and prior academic performance using linear mixed models. Data were available for 1461 (83.1%) students learning online and 298 (16.9%) students learning in person. After adjusting for sex, race/ethnicity, age, quantitative GRE score, undergraduate GPA, and math refresher score, we found quiz scores for students learning online were about 2.5% lower than those for students learning in person, on average, with a 95% confidence interval ranging from 4.9% lower to 0.02% higher. Differential performance was even closer to equality for the final exam where scores for students learning online were about 0.9% higher with a 95% confidence interval ranging from a 3.9% reduction to 5.8% improvement. These estimates suggest comparable student performance can be achieved in a graduate-level introductory biostatistics course among students learning online and in person. Supplementary materials for this article are available online.