This study aimed to characterize postoperative infection rate among patients undergoing definitive fixation of both open and closed fractures during the same surgery. Outcomes between patients with open fractures (OF) treated first were compared to those with closed fractures (CF) treated first. We identified 303 adult patients with multiple (≥ 2) pelvis and extremity fractures who presented to our Level 1 Trauma hospital in 2017. Forty patients with at least one open and one closed fracture treated with operative fixation during the same surgery were included in analysis. Eight surgical site infections (SSI) developed in seven patients. There was no significant difference between treatment order groups (OF = 4 patients (5 fractures), CF = 3 patients (3 fractures); p > 0.99). This is the first study comparing different chronologies of operative fixation in coexisting open and closed fractures. Our study shows that the choice of treatment order does not influence SSI risk. (Journal of Surgical Orthopaedic Advances 31(3):181-186, 2022).