The objective of the study was to evaluate the efficacy of intramuscular penicillin: mixture of benzyl penicillin and procain penicillin (2 MU x 2 times daily) and intravenous benzyl penicillin (4 MU x 6 times daily) in the treatment of hospitalized adult patients with erysipelas. A prospective randomized unicentric trial was conducted. In total, 112 patients entered the study; 57 in the intramuscular group and 55 patients in the intravenous group completed the trial. The failure rate was 14% for intramuscular group and 20% for the intravenous group (P = 0.40). Local complications such as of the leg abscesses were observed in the two groups (intravenous 9.1%, intramuscular 7%; P = 0477). Of the patients treated with intravenous benzyl penicillin, 25.5% presented complications related to the route (venitis). Intramuscular penicillin should be considered an effective and well-tolerated treatment of erysipelas in adult patients.