BACKGROUND: The Prospective Evaluation of Pacemaker Lead Endocarditis study is a multicenter, prospective survey of the incidence and risk factors of infectious complications after implantation of pacemakers and cardioverter-defibrillators. METHODS AND RESULTS: Between January 1, 2000, and December 31, 2000, 6319 consecutive recipients of implantable systems were enrolled at 44 medical centers and followed up for 12 months. All infectious complications were recorded, and their occurrence was related to the baseline demographic, clinical, and procedural characteristics. Among 5866 pacing systems, 3789 included 2 and 117 had >2 leads; among 453 implantable cardioverter-defibrillators, 178 were dual-lead systems. A total of 4461 de novo implantations occurred and 1858 pulse generator or lead replacements. Reinterventions were performed before hospital discharge in 101 patients. Single- and multiple-variable logistic regression analyses were performed to identify risk factors; adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. At 12 months, device-related infections were reported in 42 patients (0.68%; 95% CI, 0.47 to 0.89). The occurrence of infection was positively correlated with fever within 24 hours before the implantation procedure (aOR, 5.83; 95% CI, 2.00 to 16.98), use of temporary pacing before the implantation procedure (aOR, 2.46; 95% CI, 1.09 to 5.13), and early reinterventions (aOR, 15.04; 95% CI, 6.7 to 33.73). Implantation of a new system (aOR, 0.46; 95% CI, 0.24 to 0.87) and antibiotic prophylaxis (aOR, 0.4; 95% CI, 0.18 to 0.86) were negatively correlated with risk of infection. CONCLUSIONS: This study identified several factors of risk of device infection and confirmed the efficacy of antibiotic prophylaxis in recipients of new or replacement pacemakers or implantable cardioverter-defibrillators.