Of 167 patients treated for PJI, 76 had multiple prosthetic joints. Thirteen percent (10/76) developed a PJI in a second location. Excluding simultaneous infections, the rate was 8.3% (6/72), despite having a 57% incidence of immunosuppression, diabetes, renal failure, smoking, or steroid use. Average follow-up for patients with 1 PJI was 4.6 years (range 0.03-13.6). Seventy percent (7/10) of patients with multiple infections were bacteremic at the time of initial infection compared to 18.1% (12/66) of patients with a single infection (P = .0004). Excluding the 4 simultaneous infections (all bacteremic), the risk of developing an infection in a second joint was 20% if bacteremic and 5.2% if not bacteremic.