For first-line HIV treatment, US treatment guidelines state that efavirenz (EFV) is the only preferred non-nucleoside reverse transcriptase inhibitor (NNRTI) while nevirapine (NVP) is listed as an acceptable NNRTI.  Generic versions of NVP were first approved in the US in May 2012.  OBJECTIVES: To assess the cost-effectiveness of EFV compared with generic NVP in first-line HIV treatment in the US. METHODS: A micro-simulation state transition model was constructed to estimate the costs (2012 US$) and clinical outcomes for antiretroviral naïve HIV patients initiating EFV or NVP.  Efficacy and safety data was based on the HIV Causal Collaboration Study and a Cochrane Review.  Published sources were used to identify other inputs.  Costs included antiretroviral drug acquisition, disease management (based on CD4 counts) and adverse events. Health utility was based on CD4 counts and adverse events.  A 3% discount rate was used for costs and quality-adjusted life years (QALYs). Results are based on 100,000 micro-simulation trials with a ten year time horizon. RESULTS: Over a 10-year period, EFV was dominant over NVP in the base case with lower total costs ($346,932 vs. $364,475), modestly higher QALYs (6.795 vs. 6.782), and similar life expectancy (9.346 vs. 9.342 years).  Keeping all other inputs constant, EFV was dominant over generic NVP until the price of NVP was reduced to 50% of its base case value.  Giving EFV and NVP equal probability of treatment success but maintaining basecase adverse event rates and costs resulted in an incremental cost effectiveness ratio of $4,438 for EFV compared to NVP. CONCLUSIONS: Over a 10-year time horizon, EFV was predicted to be cost-saving compared to generic NVP with modestly higher QALYs and similar life expectancy in HIV patients initiating first-line treatment in the US. Sensitivity analysis indicated results were not sensitive to NVP price changes.