The purpose of this study was to determine the risk of periprosthetic infection after primary shoulder arthroplasty (SA) in patients undergoing previous nonarthroplasty shoulder surgery compared with those without previous surgery.All patients undergoing primary SA at our institution between 1970 and 2012 were included in this study. The cohort consisted of 4577 patients treated with 2890 total SAs, 1233 hemiarthroplasties, and 454 reverse SAs; 813 (18%) patients had undergone prior nonarthroplasty shoulder surgery on the operative side. Patients with and without previous surgery were compared for postoperative periprosthetic infection. Univariate and multivariable analyses were used.Deep postoperative infection of the shoulder was diagnosed in 68 patients (1.49%). Of the 813 patients who had undergone previous surgery, 20 (2.46%) developed a deep postoperative infection. However, of the 3764 patients who did not have previous shoulder surgery, 48 patients (1.28%) sustained deep shoulder infection. This difference was significant in both the univariate (P = .0094) and multivariate analyses (P = .0390). In addition, older age and female gender were significantly associated with a lower risk of deep postoperative infection (P = .0150 and P = .0074, respectively). A higher number of previous surgeries was also significantly associated with an increased risk of deep postoperative infection (P = .0272).The risk of infection after primary SA is significantly higher in patients with a history of prior non–arthroplasty-related surgery. This finding should be discussed with the patients before their surgery, and potential preoperative and intraoperative workup should be undertaken to identify at-risk patients.