The carbapenem antibiotic ertapenem has been shown to be safe, well tolerated and effective in treating adults with complicated urinary tract infection, skin and soft-tissue infection and community-acquired pneumonia. In this study, we evaluated ertapenem for treating these infections in children in a randomised, double-blind, active-controlled clinical trial. The primary outcome was the incidence of clinical and laboratory drug-related serious adverse events (AEs). Children were randomised in a 3:1 ratio (ertapenem:ceftriaxone) stratified by index infection and age to receive ertapenem or ceftriaxone; 303 children received ertapenem and 100 children received ceftriaxone. The median duration of parenteral therapy was 4 days for both treatments. The most commonly reported drug-related clinical AEs during parenteral therapy were diarrhoea (5.9% ertapenem, 10% ceftriaxone), infusion site erythema (3% ertapenem, 2% ceftriaxone) and infusion site pain (5% ertapenem, 1% ceftriaxone). One child in each group reported a serious drug-related clinical AE. No serious drug-related laboratory AEs were reported. In children aged 3 months to 17 years, ertapenem was well tolerated and had a comparable safety profile to that of ceftriaxone.