High rates of postoperative wound infection (POWI) have been reported after surgery for calcaneal fractures. This is a retrospective cohort study to determine the causative pathogens of these infections and subsequent treatment strategies. In addition, microbacterial growth from superficial wound swabs and deep fluid or tissue cultures were compared. Patients with a unilateral surgically treated calcaneal fracture during a 15-year period were included. Patient, fracture, and surgical characteristics were collected from the electronic medical records. An infection was categorized as deep or superficial using the Centers for Disease Control and Prevention criteria. Secondary outcomes were wound edge necrosis and wound dehiscence. The collection of culture swabs, their results, and treatment strategies were documented. Of 357 patients, 92 (26%) developed a POWI; 55 (60%) deep and 37 (40%) superficial. The most frequent causative pathogens were Enterobacteriaceae and Staphylococcus aureus. Of the 55 patients with deep infection, 31 (56%) were treated with intravenous antibiotics and surgical debridement, 2 (4%) with intravenous antibiotics, and 22 (40%) with implant removal. In 33 of 92 patients (36%) with a POWI, both superficial and deep cultures were obtained, with a microorganism not cultured from the superficial swab 13 (39%) times. In conclusion, we found that one quarter of patients with operative calcaneal fracture treatment developed a POWI, mainly caused by Enterobacteriaceae or S. aureus. Physicians should not rely on the results of superficially obtained cultures for adequate treatment of deep infection. Because the spectrum of sensitivity profiles varies greatly between hospitals and countries, we recommend empiric antibiotic treatment of both gram-positive and gram-negative microorganisms on suspicion of deep infection.