In a randomized prospective study ampicillin/sulbactam and cefamandole were compared in the therapy of patients hospitalized with community acquired pneumonia. Patients receiving ampicillin/sulbactam (n = 37) and cefamandole (n = 38) were similar with respect to age (mean age 70 vs. 76 years respectively), clinical characteristics, severity of illness and underlying disease. Pathogens isolated from patients in the cefamandole and ampicillin/sulbactam group, respectively, were Streptococcus pneumoniae (7 vs. 7 patients), Haemophilus parainfluenzae (7 vs. 6 patients), Haemophilus influenzae (5 vs. 5 patients), Staphylococcus aureus (5 vs. 4 patients), Escherichia coli (4 vs. 4 patients), Klebsiella pneumoniae (3 vs. 3 patients), Enterobacter spp. (2 vs. 3 patients), Moraxella catarrhalis (1 vs. 2 patients), and organisms of the oral flora (4 vs. 3 patients). The rate of resistance to penicillin was 80%, to clindamycin 76%, to erythromycin 45%, to ampicillin 43%, and to cefazolin 18%. Overall successful treatment rates of 81% for cefamandole and 97% for ampicillin/sulbactam (p = 0.05) were observed. Both cefamandole and ampicillin/sulbactam were shown to be effective agents for therapy of community acquired pneumonia; however ampicillin/sulbactam demonstrated superior overall clinical efficacy.