OBJECTIVES: To estimate the cost of virologic failure with the treatment of etravirine and raltegravir in multi-experienced patients in the Brazilian National AIDS Program. METHODS: Treatment regimens of etravirine and raltegravir were defined by the guidelines of the Brazilian National AIDS Program. Upon virologic failure, subsequent treatments were defined according to the same guidelines considering new drug combinations not yet used by the patients. Treatment costs considered the cost of medication as purchased by the Brazilian government and published on their website. As maraviroc, a rescue treatment, is not yet reimbursed by the AIDS program, its price was defined by law. To estimate the total cost, patient numbers were calculated by the number of capsules of raltegravir dispensed in the past 96 weeks, and assumed the same for patients treated with etravirine. Virologic failure was gathered from the phase III clinical trials of raltegravir and etravirine at week 48 and week 96. RESULTS: The average cost of treatment for multi-failure patients with etravirine was on average R$ 26.692,26 at week 48 of treatment compared to R$ 26.634,15 per patient treated with raltegravir. At week 96, the average treatment cost per patient was R$ 56.810,59 for raltegravir and R$ 53.904,30 for etravirine. Given that 3.942 patients received treatment in the previous 98 weeks, around 1.301 patients will fail treatment with raltegravir and 630 with etravirine. The total cost of treating these patients is R$ 73 million for raltegravir and R$ 34 million for etravirine. CONCLUSIONS: Despite a similar average cost at week 48, etravirine treatment is a more economic option for the treatment of multi-failure patients compared to raltegravir, saving up to 50% of treatment costs with virologic failure patients in the Brazilian National AIDS program over 96 weeks. Virologic failure is therefore an important indicator to avoid subsequent treatment costs especially in the long-term.