OBJECTIVE: To evaluate the cost-effectiveness of financial incentives for human immunodeficiency virus (HIV) viral suppression compared to standard of care. STUDY DESIGN: Mathematical model of 2-year intervention offering financial incentives ($70 quarterly) for viral suppression (<400 copies/ml(3)) based on the HPTN 065 clinical trial with HIV patients in the Bronx, NY and Washington, D.C. METHODS: A disease progression model with HIV transmission risk equations was developed following guidelines from the Second Panel on Cost-Effectiveness in Health and Medicine. We used health care sector and societal perspectives, 3% discount rate, and lifetime horizon. Data sources included trial data (baseline N = 16,208 patients), CDC HIV Surveillance data, and published literature. Outcomes were costs (2017 USD), quality-adjusted life years (QALYs), HIV infections prevented, and incremental cost-effectiveness ratio (ICER). RESULTS: Financial incentives for viral suppression were estimated to be cost-saving from a societal perspective and cost-effective ($49,877/QALY) from a health care sector perspective. Compared to the standard of care, financial incentives gain 0.06 QALYs and lower discounted lifetime costs by $4210 per patient. The model estimates that incentivized patients transmit 9% fewer infections than the standard-of-care patients. In the sensitivity analysis, ICER 95% credible intervals ranged from cost-saving to $501,610/QALY with 72% of simulations being cost-effective using a $150,000/QALY threshold. Modeling results are limited by uncertainty in efficacy from the clinical trial. CONCLUSIONS: Financial incentives, as used in HTPN 065, are estimated to improve quality and length of life, reduce HIV transmissions, and save money from a societal perspective. Financial incentives offer a promising option for enhancing the benefits of medication in the United States.