Objective: To examine how in-person classroom instruction was related to risk of SARS-CoV-2 infection in undergraduate students. Participants: Indiana University undergraduate students (n = 69,606) enrolled in Fall 2020, when courses with in-person and remote instruction options were available. Methods: Students participated weekly in mandatory SARS-CoV-2 RT-PCR asymptomatic testing by random selection, supplemented with symptomatic testing as needed. We used log-binomial regression models to estimate the association between number of in-person credit hours and the risk of SARS-CoV-2 infection over the course of the semester. Results: Overall 5,786 SARS-CoV-2 cases were observed. Increased in-person credit hour exposures were not associated with increased risk of SARS-CoV-2 overall [aRR (95% CI): 0.98 (0.97,0.99)], nor within specific subgroups (Greek affiliation and class). Conclusions: In-person instruction did not appear to increase SARS-CoV-2 transmission in a university setting with rigorous protective measures in place, prior to mass vaccine rollout and prior to delta variant emergence.