OBJECTIVES Approximately 483 patients in Slovakia are living with HIV, with 68 new infections in 2013. Raltegravir (RAL) is reimbursed for HIV-1-infected treatment-naive (TN) and treatment-experienced (TE) patients in Slovakia. The objective of this analysis was to determine the cost-effectiveness of dolutegravir (DTG) relative to RAL. METHODS This study is based on the Anti-Retroviral Analysis by Monte Carlo Individual Simulation model. A microsimulation approach simulates the outcome of anti-retroviral therapy by following virological suppression and CD4+ cell count throughout patients’ lifetime. Each treatment was assigned its specific efficacy, adverse events rates, and cardiovascular risk according to lipid parameters evolution; and costs and quality of life values were allocated by CD4+ cell count categories and attached to specific events. The analysis was performed from payer’s perspective in Slovak settings. RESULTS Over a lifetime, in TN patients the estimated total costs for the DTG strategy compared with the RAL were lower (220,731€ versus 222,079€). The savings for DTG are mostly associated to the lower drug acquisition cost. The life expectancy was similar for the DTG and RAL (31.23 years and 30.82 years). This translated into 0.057 QALYs. DTG was dominant treatment strategy in TN patients. In TE patients, the estimated total costs were slightly higher for the DTG strategy compared with the RAL (192,682€ versus 188,059€). These additional costs for the DTG are related to patients living longer with DTG over RAL (19.16 years versus 18.30 years). An increment of 0.275 QALYs for DTG was gained. The ICUR for the comparison of DTG and RAL was 16,805 € per QALY, which is below the threshold 19,320€ defined as the limit at which an intervention would be considered as cost-effective in Slovakia. CONCLUSIONS At the proposed price and when compared to RAL, DTG is dominant in TN patients and cost-effective in TE patients.