OBJECTIVES: To investigate the impact of patients´ compliance on cost effectiveness of the following oral antibacterials in inpatient treatment of mild to moderate superficial skin and soft-tissue (SST) infections from the perspective of hospitals in Germany: amoxicillin/clavulanic acid 500/125mg thrice daily (AMC); cefpodoxime proxetil 200mg twice daily (CPD); cefuroxime axetil 500mg twice daily (CXM); ciprofloxacin 500mg twice daily (CIP); or roxithromycin 300mg once daily (ROX). METHODS: An economic model was used to quantify the cost-effectiveness ratio (CER) `cost per successfully treated patient´ of each alternative, based on decision-tree technique synthesizing published data, the results of a hospital survey and expert knowledge. Costs were exclusively those incurred by hospitals. The method of the total differential then was used to quantify the impact of the respective compliance rate on the CER of each alternative based on average values of the model parameters. RESULTS: There were 3 groups of CERs: 105 DM (ROX) with once, between 175 and 193 DM (CXM, CPD, CIP) with twice, and 265 DM (AMC) with thrice daily application. The application-specific compliance rate had by far the greatest impact on each CER. This impact was about 1.5- to 3-fold of that of the clinical effectiveness and about 1.9- to 4.7-fold of that of the acquisition cost per unit of each alternative. In the sensitivity analysis, the robustness of the model was shown in a Monte Carlo simulation. After 10,000 computations each, the cost-effectiveness acceptability curves of the alternatives again showed 3 distinct groups. Once daily application (ROX) with the highest compliance rate was most favourable followed by twice (CXM, CPD, CIP) and thrice (AMC) daily application with moderate and low compliance, respectively. CONCLUSIONS: Choosing an alternative associated with high compliance or improving patients´ compliance highlight an important saving potential for hospitals in the treatment of SST infections.