Background: Totally implantable venous access devices (TIVADs) are frequently used in pediatric patients with cancer owing to their multiple benefits. Despite occasional infections with TIVADs, knowledge of the incidence and risk factors is limited. Methods: This retrospective study included pediatric patients with cancer who received TIVAD at Chungbuk National University Hospital from 2001 to 2018. We collected data on demographics, diagnosis, duration of TIVAD use, pathogens, and other risk factors. Results: During the study period, 47 TIVADs with 20,770 device-days were applied in 42 patients. There were 14 TIVAD infections (14/47, 29.8%), with an infection rate of 0.25 infections per TIVAD per year (0.69 cases/1000 device-days). TIVAD infections occurred at a median of 5.5 months (range, 8 days–30 months) after insertion. The most common causative microorganisms were methicillin-resistant coagulase-negative staphylococci (n = 8, 57.1%) followed by Escherichia coli and Streptococcus mitis (n = 2, each). A platelet count below 150,000/μL at the time of TIVAD insertion and diagnosis of acute lymphoblastic leukemia (ALL) were the major risk factors for TIVAD infection. Device removal was the mainstay of treatment (11/14, 78.6%). Conclusion: TIVAD insertion was safe and dependable in children with malignancies. Risk factors for TIVAD infection included a platelet count below the normal range at the time of device insertion and a diagnosis of ALL. Further studies are needed to identify preventive factors against TIVAD infections in children with cancer.