OBJECTIVES: Therapeutic reference pricing (TRP) is one of the most frequently employed methods for cost-containment of pharmaceuticals. The Hungarian National Health Insurance Fund (NHIF) applies TRP based on DDD, yet even the WHO objects to using DDD in pricing and reimbursement decisions. Our objective was to compare actual drug use to DDD and to evaluate whether TRP based on DDD could result in savings in the costs of maintenance medication and the total direct health expenditures between asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED). METHODS: Real world data for the analysis was derived from the NHIF database. Actual drug use and average costs were compared in four groups (high dose SYT, medium dose SYT, high dose SED and medium dose SED). Multiple linear regression was employed to adjust data for the differences in gender and age distribution of patients. RESULTS: A total of 12,260 patients using SED and 15,539 patients using SYT for asthma were involved into the analysis. Average drug use was lower in both groups than DDD. Patients used 1.38-1.95 inhalations in both SED groups, 1.28-1.97 inhalations in the high dose SYT group, and 1.74-2.49 inhalations in the medium dose SYT group. Although the daily therapeutic cost of medium dose SED based on DDD would be much lower than the cost of SYT, no difference was found in the actual cost of the maintenance therapy or the total medical costs. CONCLUSIONS: Our analysis provides evidence about the limitation of employing daily therapy costs according to DDD for TRP. No relationship was found between the daily therapeutic costs calculated using the NHIF methodology and costs of real drug use, in real world TRP did not lead to the reduction of expenditures from the payer' perspective. Potential confounding factors may limit the generalizability of conclusions.