Objective: To document the incidence of postoperative wound complications associated with the use of rhBMP-2 in a large series of patients for both acute traumatic and reconstructive extremity cases. Design: Retrospective chart and radiographic review. Setting: Level I trauma center. Methods: A retrospective chart and x-ray review was performed on cases between 2002 and 2009, in which rhBMP-2 (Infuse) was used in acute trauma or posttraumatic reconstruction. The following data points were collected: age, surgical site, purpose (acute vs. reconstructive), associated wound factors (open fractures, soft tissue injury requiring coverage, or history of infection), signs of infection (seroma, erythema, prolonged drainage, abscess), reoperation rate secondary to wound complication, culture results, and union. These cases were then compared with a matched cohort without the use of bone morphogenetic protein-2 (matched for age, type of case, anatomic site, and open injury) for statistical analysis. Results: Group 1 was comprised a total of 193 patients whose treatment included rhBMP-2 (155 reconstructive and 38 acute open fractures). Group 2 was comprised 181 patients treated without the use of rhBMP-2 (145 reconstructive and 36 acute open fractures). The incidences of documented wound complications were 31% (60/193) in group 1 and 18% (33/181) in group 2 (P = 0.004). Reoperation rates for wound complications were in 3.1% of group 1 and 8.3% of group 2 (P = 0.04). Age, sex, anatomic site, acute trauma, open fracture, and the need for soft tissue reconstruction did not correlate with the need to return to the operating room for presumed or actual wound infection. The rates of union between rhBMP-2 and control groups were 90% versus 74% (P < 0.001); for acute trauma cases, 94% versus 79% (P = 0.220); and for reconstructive cases, 89% versus 73% (P = 0.002). Conclusions: The use of rhBMP-2 in both acute traumatic and posttraumatic reconstructive extremity surgery may increase the incidence of prolonged postoperative serous wound drainage. However, this does not seem to correlate with an increased incidence of postoperative wound infection or the need for reoperation. The use of rhBMP-2 seems to have a beneficial effect in improving union rates for both acute trauma and posttraumatic reconstruction of the extremities (P = 0.002); however, this and the mechanism for prolonged serous drainage require further study before definitive recommendations can be made.