In this comparative study, both cefmetazole and cefoxitin were found to be safe and effective in the treatment of skin and soft tissue infections. Greater activity of cefmetazole against some strains of Staphylococcus aureus, Streptococcus pneumoniae, beta-haemolytic streptococci and aerobic Gram-negative bacilli was confirmed. A 90% or better cure rate was achieved with both drugs. At late follow up, three patients treated initially with cefmetazole had recurrent signs and symptoms. However, these three patients had vascular insufficiency which predisposed them to infection. Since cefmetazole has a longer half-life than cefoxitin, it may prove to be more convenient, or more cost effective, or both, in these and other infections.