OBJECTIVES: Compare the cost-efectiveness (CE) of levodopa, pramipexole, rasagiline and selegiline in patients with early Parkinson’s disease from the perspective of National Institute of Neurology and Neurosurgery (NINN) in Mexico. METHODS: We developed a CE model, that linked Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II (activities of daily life) and III (motor) scores to disease progression and direct costs (drugs, medical appointments, adverse events, and laboratory studies), which were obtained of clinical records and unit cost of NINN. Data used in the model were obtained from clinical trials and we developed an indirect comparison to evaluate the efficacy and safety, with the study of Jiao and cols., an hypothetical cohort were placed in accordance with this efficacy and the Hoehn and Yahr states, an analysis of incremental cost-effectiveness ratio (ICER) was performed. We used a markov model to estimate the CE and performed sensitivity analyses and varying disease progression parameters and costs. The outcome of effectiveness was  life years gained. RESULTS: For patients with early PD in monotherapy, treatment with levodopa had lower costs and more effectiveness than pramipexole, rasagiline and selegiline treatments. With a time horizon of 5 years, levodopa was 5.04  life years gained and cost $236,750.52, the cost of selegiline was $247,094.21 with 4.1  life years gained, pramipexol had a cost of $247,420.46 with 4.1  life years gained and finally rasagilina $254,006.56 with 3.17  life years gained, all values of ICER were less than one GDP per capital. This results showed that levodopa was the dominant alternative. The sensitivity analyses confirm the results. CONCLUSIONS: Findings of this study indicate that levodopa provides the major effectiveness and the lower cost compared to pramipexole, rasagiline and selegiline as first treatment option in patients with early Parkinson disease (measured by UPDRS) in monotherapy.