The aim of the study was to evaluate the efficacy and safety of cefadroxil once daily as compared to flucloxacillin twice daily in skin and soft tissue infections. The patients were given either Cefamox 1 g once daily or Heracillin 1.5 g (tablets twice daily or suspension three times daily) for 10 days in this randomized single-blind multicentre study. Of 661 patients aged 3–81 years, 651 qualified for the evaluation of adverse events, 642 for the intention-to-treat analysis of efficacy and 327 for the primary statistical evaluation of efficacy. The incidence of adverse events was similar for both drugs (cefadroxil 30%, flucloxacillin 36%). The clinical results of the treatments were satisfactory, with 97% of the patients being healed or improved in both groups. Treatment with cefadroxil 1 g once daily was equivalent to flucloxacillin twice or three times daily in the treatment of skin and soft tissue infections.