On-demand pre-exposure prophylaxis (PrEP) taken before and after sex is a popular and effective HIV prevention option, researchers reported at the virtual International AIDS Conference in July. Although this schedule, also known as PrEP 2-1-1, is not yet approved by the Food and Drug Administration, some providers are already offering it, including Magnet, the nurse-led sexual health clinic run by the San Francisco AIDS Foundation. Among 828 people starting PrEP for the first time who were offered the choice, 30% chose to take Truvada (tenofovir disoproxil fumarate/emtricitabine) as PrEP 2-1-1 over a daily dose. Among 1,703 current daily PrEP users, 21% decided to switch. Overall, 24% chose PrEP 2-1-1, and 3% said they had sought PrEP only because the new option was available. Both strategies proved highly effective, and adherence was high. New HIV diagnoses were rare in both groups and were linked to poor adherence. Side effects were uncommon overall but occurred more often in the PrEP 2-1-1 group.