OBJECTIVE: To compare the risk of coronavirus disease 2019 (COVID-19) outcomes by antiretroviral therapy (ART) regimens among men with HIV. DESIGN: We included men with HIV on ART in the Veterans Aging Cohort Study who, between February 2020 and October 2021, were 18 years or older and had adequate virological control, CD4 + cell count, and HIV viral load measured in the previous 12 months, and no previous COVID-19 diagnosis or vaccination. METHODS: We compared the adjusted risks of documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19-related hospitalization, and intensive care unit (ICU) admission by baseline ART regimen: tenofovir alafenamide (TAF)/emtricitabine (FTC), tenofovir disoproxil fumarate (TDF)/FTC, abacavir (ABC)/lamivudine (3TC), and other. We fit pooled logistic regressions to estimate the 18-month risks standardized by demographic and clinical factors. RESULTS: Among 20 494 eligible individuals, the baseline characteristics were similar across regimens, except that TDF/FTC and TAF/FTC had lower prevalences of chronic kidney disease and estimated glomerular filtration rate <60 ml/min. Compared with TAF/FTC, the estimated 18-month risk ratio (95% confidence interval) of documented SARS-CoV-2 infection was 0.65 (0.43, 0.89) for TDF/FTC, 1.00 (0.85, 1.18) for ABC/3TC, and 0.87 (0.70, 1.04) for others. The corresponding risk ratios for COVID-19 hospitalization were 0.43 (0.07, 0.87), 1.09 (0.79, 1.48), and 1.21 (0.88, 1.62). The risk of COVID-19 ICU admission was lowest for TDF/FTC, but the estimates were imprecise. CONCLUSION: Our study suggests that, in men living with HIV, TDF/FTC may protect against COVID-19-related events. Randomized trials are needed to investigate the effectiveness of TDF as prophylaxis for, and early treatment of, COVID-19 in the general population.