Despite high need, HIV preexposure prophylaxis (PrEP) utilization among people who use drugs (PWUD) remains low. Boston Health Care for the Homeless Program implemented an innovative "low-threshold" PrEP Program for PWUD experiencing homelessness in Boston, Massachusetts. From October 1, 2018 to February 29, 2020, 239 clients were linked to PrEP services, and 152 were prescribed PrEP (mean = 8.9/month), over twice the number of PrEP prescriptions over the previous 12 months (n = 48; mean = 4/month). The cumulative probability of remaining on PrEP for 6 months was 44% (95% confidence interval = 36%, 52%).