The purpose of this study was to elucidate the risk factors for surgical-site infection (SSI) in oral cancer surgery with microvascular free-flap reconstructions and to propose appropriate SSI prevention. There were 276 patients who underwent oral cancer surgery with microvascular free-flap reconstructions at the Department of Oral and Maxillo-facial Surgery of Tokai University Hospital. The following variables were assessed as risk factors for SSIs: preoperative variables, including age, sex, body mass index, American Society of Anesthesiologist’s (ASA) score, debilitating comorbidities, smoking, alcohol consumption, and Union Internationale Contre le Cancer Tumor Node Metastasis (UICC-TNM) classification; and operative variables, including duration of surgery, amount of blood loss, quantity of blood transfusion, tracheostomy, area of neck dissection, and previous chemotherapy. Statistical analysis was conducted to determine whether these factors constitute risks for SSI. Total overall SSI rate was 40.6% (112/276). When the occurrence of SSI was compared with the variables, ASA score (P = 0.036), T stage (P = 0.013), duration of surgery (P < 0.001), blood loss (P = 0.001), blood transfusion (P = 0.01), and area of neck dissection (P = 0.009) showed statistical significance. Analysis of these variables with a logistic regression model yielded ASA score and duration of surgery as significant factors. There was a tendency for blood loss and duration of surgery to increase in patients with a high T stage. A high T stage not only broadens the resection area and increases surgical invasiveness, it also increases susceptibility to dead space after microvascular reconstruction for oral cancer. Particular care in treating the wound should be taken in surgical patients with high T-stage scores. The occurrence of SSI is of particular concern in oral cancer surgery in patients with high ASA scores.