Background: Trauma is defined by the NHSN as “blunt or penetrating traumatic injury.” Therefore, if the surgery was performed because of a recent fall, for example, then it is a trauma surgery. Here, we investigated which preoperative and operative parameters are associated with surgical site infection (SSI) after orthopedic trauma surgery. Objective: We aimed to answer 3 main questions: What is the risk of wound infection for patients undergoing trauma surgery? What are the main etiologic agents of SSI after trauma surgery? And what are the risk factors associated with SSI after trauma surgery? Methods: This prospective multicenter cohort study included 2,035 patients undergoing trauma surgery between July 2016 and June 2018 in 4 hospitals in Belo Horizonte, Brazil. Outcome variables were SSI, hospital mortality, and length of hospital stay. The following preoperative and operative parameters were evaluated: age, length of hospital stay before surgery, duration of surgery, number of professionals at surgery, number of hospital admissions, surgical wound classification, American Society of Anesthesiologists (ASA) preoperative assessment score, type of surgery (elective, emergency), general anesthesia (yes, no), trauma surgery (yes, no), and the 3-point prediction Nosocomial Infections Surveillance (NNIS) risk index. Results: The overall estimated SSI risk was 2.8% (95% CI, 2.0%–3.6%). Hospital mortality risk after trauma surgery was 3.4% (95% CI, 2.8%–4.4%). Hospital length of stay parameters in noninfected patients were as follows: mean, 8 days; median, 3 days; SD, 12 days. Hospital length of stay parameters in infected patients were mean, 30 days; median, 23 days; with SD, 31 days. The parameters for hospital stay in infected patients were mean, 10 days; median, 3 days, and SD, 15.9 (P < .001). Trauma orthopedic surgery lasting >2 hours was associated with approximately twice the risk (RR, 2.2) of developing an SSI compared to ≤2 hours of surgery: 27 of 739 (3.7%) versus 21 of 1,290 (1.6%), respectively, (P = .005) (Fig. 1). The NNIS risk index predicts the risk of SSI after trauma surgery (P = .003): 13 of 737 SSIs (1.8%) had an NNIS risk index of 0; 20 of 736 SSIs (2.7%) had an NNIS risk index of 1; 8 of 211 SSIs (3.8%) had an NNIS risk index of 2; and 2 of 11 SSIs (18.2%) had an NNIS risk index of 3 (Fig. 2). Conclusions: We identified intrinsic risk factors for SSI after orthopedic trauma surgery. The identification of the actual SSI incidence after trauma surgery in developing country hospitals and associated risk factors may support actions to minimize the complications caused by SSI.