PURPOSE: The CDC recommends routine voluntary HIV testing of all patients. HIV testing rates however are low even among those at identifiable risk. Once tested, many patients do not return to receive their results. Nurse-initiated testing, streamlined counseling, and rapid testing have been proposed as strategies to increase testing rates and receipt of results. The cost effectiveness of these strategies is uncertain. METHODS: As part of a randomized controlled trial, we evaluated costs, quality of life, and survival for patients who underwent either: (1) traditional counseling and HIV testing initiated by physicians (PHYSICIAN-TRADITIONAL); (2) nurse-initiated opt-out screening with traditional counseling and testing (NURSE-TRADITIONAL); or (3) nurse-initiated opt-out screening with streamlined counseling and rapid testing (NURSE-RAPID). Acceptance of testing and return rates were based on the RCT trial of 251 patients at two VA clinics (HIV prevalence = 0.4%). Long-term cost and health outcomes were based on the Markov model that simulated outcomes over the lifetime of the patient. We assumed identified patients started treatment according to current guidelines. Disease progression was modeled based on CD4 and viral load levels. RESULTS: In the trial, 41% of patients in the PHYSICIAN-TRADITIONAL strategy received HIV testing and 35.3% of these patients returned for their results. The NURSE-TRADITIONAL strategy had higher testing rates (84.5%) but only 36.6% received their results. In the NURSE-RAPID strategy, 89.3% of patients received testing, 89.3% received their results. Our analysis estimated that patients in the PHYSICIAN-TRADITIONAL strategy had a lifetime cost of $48,656 and a quality-adjusted life expectancy (QALE) of 16.271 years. The NURSE-TRADITIONAL strategy increased costs by $53 and QALE by 0.48 days. Patients in the NURSE-RAPID strategy cost $66 more than those in the PHYSICIAN-TRADITIONAL strategy with a 0.66 day increase in QALE for an incremental cost-effectiveness of $36,400/QALY. The NURSE-TRADITIONAL strategy was less effective than the NURSE-RAPID strategy and had a less favorable incremental cost-effectiveness ratio. Including the costs and benefits of transmission, the cost-effectiveness of NURSE-RAPID relative to PHYSICIAN-TRADITIONAL became more favorable ($10,689/QALY). Results were modestly sensitive to the prevalence of HIV and testing costs. CONCLUSIONS: Nurse-initiated streamlined counseling with rapid testing was cost-effective compared with traditional testing strategies and should be considered by clinical managers and policymakers when implementing HIV testing into primary or urgent care.