We compared aspoxicillin, a new broad-spectrum penicillin derivative, with piperacillin in severe abdominal infection. Aspoxicillin 4 g administered tds (n = 52) or piperacillin 4 g qds (n = 53) usually as monotherapy were randomly given to patients suffering from perforated appendicitis, acute cholecystitis, ulcer or colon perforation, or intra-abdominal abscess. Blood, tissue and exudate cultures were obtained when applicable for pathogen identification and susceptibility testing. The efficacy rates were similar in the two study groups. Of the 50 evaluable aspoxicillin patients 45 (90%) were considered as treatment responders compared with 48 patients out of 53 (91%) in the piperacillin group (NS). The 95% confidence interval for the efficacy difference was -12% to +11% thus showing no difference between the two drugs. Both drugs were generally well tolerated and no serious drug-related adverse events were noted. However, five patients died because of their illness and one patient had a fatal myocardial infarction. In conclusion, aspoxicillin 4 g tds was shown to be equal to piperacillin 4 g qds in severe abdominal infections.