Infection is the most frequent complication associated with the use of totally implantable venous access port (TIVAP). This retrospective study was conducted to determine the risk factors affecting TIVAP-related infection. A total of 1406 patients implanted with TIVAP at our center were included in this retrospective study. Incidence of perioperative infection, patient characteristics and bacteriologic data were retrieved and analyzed. Univariable analyses and multiple logistic regression analyses were used to determine the risk factors. Overall, 72 (5.1%) patients had perioperative infection, and TIVAP was finally removed from 12 (0.85%) patients. There was significantly more hematologic malignancy in the infection group, compared to the non-infection group. Patients with chemotherapy and infection within 30 days before operation also had more infections. There were more inpatients in the infection group than in the non-infection group. The rate of hematoma was higher in the infected patients. Multivariate logistic analysis revealed that hematoma (OR 5.695, p < 0.001), preoperative hospital stay (⩾14d) (OR 2.945, p < 0.001), history of chemotherapy (OR 2.628, p = 0.002), history of infection (within 30 days) (OR 4.325, p < 0.001) were independent risk factor for infection. This study demonstrated that hematoma, preoperative hospital stay (⩾14d), history of chemotherapy and history of infection (within 30 days) are independent risk factor for all patients.