Background: The use of central venous access devices (CVADs) is of paramount importance to safely deliver antiblastic and support therapies in children with cancer. Though, in pediatric patients, as much as in adults, CVADs are potentially associated with severe complications which may result in unscheduled interruption of therapy, hospitalization, increased morbidity/mortality, and increased cost of care. Methods: We have reviewed retrospectively our experience with CVADs in children with solid tumors and hematologic diseases, with the purpose of verifying if the adoption of well-defined insertion and maintenance bundles might be effective in reducing catheter-related complications, and in particular catheter-related thrombosis. Results: A total of 227 CVADs were analyzed: 175 peripherally inserted central catheters (PICCs), 50 centrally inserted central catheters (CICCs), and 2 femorally inserted central catheters. All CVADs were non-valved, non-cuffed power injectable polyurethane catheters; 81% were tunneled. Median dwelling time of CVADs was 172 days, for a total number of 39,044 catheter days. A very low incidence of both symptomatic catheter-related thrombosis (0.9%) and catheter-related blood stream infection (0.56 episodes per 1000 catheter days) was found. Unscheduled removal or guidewire replacement because of mechanic complications occurred in 15.7% of CVADs. There was no difference in terms of complications between PICCs and CICCs or between tunneled and non-tunneled catheters. Conclusions: Our experience with CVADs in oncologic and hematologic children suggests that catheter-related complications may be minimized by the adoption of appropriate insertion and maintenance bundles.