OBJECTIVES: to compare three-years costs and effects of terbinafine 250 mg/d for 12 or 16 weeks (T12, T16) and itraconazole 400 mg/d for 1 week every 4 weeks for 12 or 16 weeks (I3, I4) and select the optimal treatment strategy for toenail onychomycosis in Poland. METHODS: Data from the literature (a search of Medline – reports with time horizon >1 year, intent-to-treat design) were used to estimate the mycological cure rate. Direct medical costs were estimated on the basis of current treatment patterns in Poland. The perspective of the health-care payers (sick fund and patients) and a time horizon of three years were taken. Costs and effects of the treatment strategies were modeled using six scenarios, which attempt to reflect real-life practice: T12 or T16 as primary treatment, I3 as treatment of failure and T12 or I3 as treatment of re-infection (T12/I3,T12; T12/I3,I3; T16/I3,T12; T16/I3,I3) and I3 or I4 as primary treatment, T12 as treatment of failure and re-infection (I3/T12, T12; I4/T12, T12). One-way sensitivity analysis and threshold analyses were performed. RESULTS: The mean cost/mycological cure (in PLN, 1 USD = 4 PLN) were: 1925 for T12/I3,T12; 1986 for T12/I3,I3; 2175 for T16/I3,T12; 2244 for T16/I3,I3; 2375 for I3/T12,T12 and 2477 for I4/T12,T12. The strategy T12/I3,I3 was dominated by T12/I3,T12. The strategies T16/I3,I3 and I3/T12,T12 were dominated by T16/I3,T12. The incremental analysis vs. strategy T12/I3,T12 indicated, that T16/I3,T12 and I4/T12,T12 were not cost-effective alternatives for T12/I3,T12 with ICER 14 743 and 19 687 PLN/mycological cure gained, respectively. Changing the values of key drivers in the sensitivity analysis did not have any significant effect on ICER. CONCLUSION: T12 as primary treatment with I3 as treatment of failure and T12 as treatment of re-infection was the most cost-effective treatment for toenail onychomycosis in Poland.