Wound complications such as surgical site infection (SSI) and dehiscence are among the most common complications of thoracolumbar spinal fusion surgery and are particularly prevalent in patients with risk factors such as obesity, diabetes, smoking, malignancy, and multilevel and/or revision procedures. A specialized wound closure technique with muscle flap mobilization, which reduces tension at the wound edges and increases the bulk of vascularized tissue in the midline, can be employed as a salvage procedure to manage wound complications. The authors evaluated the effectiveness of prophylactic muscle flap closure for reducing SSI in patients with risk factors for wound complications who undergo thoracolumbar fusion surgery. A retrospective review of thoracolumbar fusion surgeries over a 15-year period was conducted in a group of patients at risk for wound complications to compare outcomes of patients who underwent prophylactic muscle flap closure with outcomes of patients who had conventional wound closure. Patients were selected for specialized closure based upon a protocol adopted during the study period. Patients were excluded if they had active infections or underwent tubular retractor-mediated decompression and did not have open surgery with a midline incision. Of 716 patients, wound closure was performed in 455 patients using conventional closure and in 261 using muscle flap closure. There were no significant differences in the ratios of male to female patients, with 251 men and 204 women with conventional closure and 133 men and 128 women with muscle flap closure, but the muscle flap patients were older than the conventional closure patients, with mean ages of 65.2 versus 62.9 years (p < 0.005). Indications for surgery in the muscle flap group and the conventional group, respectively, were metastatic disease in 44 (17%) and 32 (7%) patients; trauma in 10 (4%) and 14 (3%) patients; and degenerative disease, including spondylolisthesis, spondylolysis, and stenosis, in 207 (79%) and 409 (90%) patients, with more muscle flap patients having metastasis (p < 0.00001). Patients having muscle flaps had significantly higher rates of diabetes, smoking, and revision surgery, and a higher mean BMI and number of operative levels. The serum albumin level was slightly lower in the muscle flap group (p < 0.047). The wound infection rate was significantly lower in the muscle flap group (0.4%) compared with the conventional closure group (2.4%) (p < 0.033). Prophylactic muscle flap closure significantly lowers the rate of SSI in patients undergoing thoracolumbar spinal fusion who harbor risk factors for wound complications, with even fewer infections seen than in a group of patients without similar risk factors. Given the success of the technique, consideration of wider use for thoracolumbar fusion cases, even those without a high level of complexity, may be warranted.