Abstract In a low-barrier, long-acting preexposure prophylaxis (PrEP) program in a safety net setting, permitting same-day or next-day initiation, 85% of injections were on time, and 6-month retention was 83%, surpassing outcomes from most previously reported oral PrEP studies. With drop-in, wraparound services, similar retention among housing-insecure populations was seen. Long-acting PrEP expansion is urgently needed.