Background: Placement of central venous access devices is a clinical procedure associated with some risk of adverse events and with a relevant cost. Careful choice of the device, appropriate insertion technique, and proper management of the device are well-known strategies commonly adopted to achieve an optimal clinical result. However, the environment where the procedure takes place may have an impact on the overall outcome in terms of safety and cost-effectiveness. Methods: We carried out a retrospective analysis on pediatric patients scheduled for a major neurosurgical operation, who required a central venous access device in the perioperative period. We divided the patients in two groups: in group A the central venous access device was inserted in the operating room, while in group B the central venous access device was inserted in the sedation room of our Pediatric Intensive Care Unit. We compared the two groups in terms of safety and cost-effectiveness. Results: We analyzed 47 central venous access devices in 42 children. There were no insertion-related complications. Only one catheter-related bloodstream infection was recorded, in group A. However, the costs related to central venous access device insertion were quite different: €330–€540 in group A versus €105–€135 in group B. Conclusion: In the pediatric patient candidate to a major neurosurgical operation, preoperative insertion of the central venous access device in the sedation room rather than in the operating room is less expensive and equally safe.