Although many academic institutions have implemented infection control and prevention protocols, including regular asymptomatic self-testing, in response to the COVID-19 pandemic, the outcomes of mandatory surveillance testing programs at academic dental institutions that offer direct patient-facing clinical care has not yet been reported. To report the findings of a comprehensive surveillance COVID-19 testing program at an academic dental institution by assessing SARS-CoV-2 positivity rates and the potential association of test positivity with individual-level characteristics such as age, sex, and role. A retrospective cohort study was conducted using SARS-CoV-2 self-testing data from a mandatory surveillance program at the Harvard School of Dental Medicine. Test results obtained between August 24, 2020, and February 28, 2022, from students, faculty, and staff members were analyzed. Testing cadence varied from 1 to 3 times per week depending on risk status. The association of individual characteristics with test positivity was evaluated with univariate analyses and a bayesian multilevel logistic regression model. Age by decade, sex, and role or position category (staff members, faculty, and students stratified by their involvement in clinical care activities), testing cadence, and testing date. Positive results from SARS-CoV-2 real-time reverse transcription-polymerase chain reaction self-tests were assessed. Of the 390 study participants, 210 (53.8%) were women. Participants were grouped by age as follows: 20 to 29 years (190 [48.7%]), 30 to 39 years (88 [22.6%]), 40 to 49 years (44 [11.3%]), 50 to 59 years (42 [10.8%]), and 60 years or older (26 [6.7%]). Test results demonstrated an overall 0.27% positivity rate (61 test-positive cases), with a peak weekly positivity rate of 5.12% in the first week of January 2022. The mean (SD) test positivity rate among those involved in clinical activities was 0.25% (0.04) compared with 0.36% (0.09) among nonclinical participants. When adjusting for all considered covariates, test positivity was significantly associated with testing frequency (3 times vs 1 time per week: odds ratio [OR], 1.51 [95% credible interval (CrI), 1.07-3.69]) and timing of the test (after vs during the Alpha wave: OR, 0.33 [95% CrI, 0.11-0.88]; and Omicron vs Alpha: OR, 11.59 [95% CrI, 6.49-22.21]) but not with individual characteristics (age, sex, and role). These findings suggest that implementing an adaptive testing cadence based on the risk status of individuals may be effective in reducing the risk of SARS-CoV-2 infection within an institution. In this study, involvement in clinical activities did not pose additional risk of SARS-CoV-2 infection compared with other in-person activities in the presence of these control measures.