The incidence of late infection of total joint prostheses is 0.6%. Because this incidence has increased from 0.08% in 1978, the authors reviewed their experience and the literature in search of pathogenetic and preventative measures. The most common pathogen responsible for late prosthetic joint infections was staphylococcus (54%; both Staphylococcus aureus and Staphylococcus epidermidis), even when infection was of dental origin. The three most common origins of infection were skin and soft tissue (46%), dental (15%), and urinary (13%). Escherichia coli was the most common pathogen when the source was the urinary tract. Mortality and cost calculations indicate that chemoprophylaxis is justified for dental procedures and probably also for other surgical procedures in organs containing microflora. Prophylaxis must include antistaphylococcal drugs. The first generation cephalosporin antibiotics are recommended.