Introduction: Over the past decades, significant efforts have been made to reduce early and late catheter-related complications in critically ill patients, using approaches based on bundles of evidence-based interventions. Methods: In this prospective clinical study, the authors evaluated the incidence of catheter-related complications in their neuro-intensive care unit during a 4-year period, adopting systematically the GAVeCeLT bundles for the insertion and management of all central venous access devices: centrally inserted central catheters (CICCs), peripherally inserted central catheters (PICCs) and femorally inserted central catheters (FICCs). All early/immediate and late complications were recorded. Results: On 486 central lines (328 CICCs, 149 PICCs and 9 FICCs), the only clinically relevant early/immediate complication was primary tip malposition (1%). In regards late infective complications, the authors did not record any case of catheter-related bloodstream infection; though, they observed one case of central line associated blood stream infection (one CICC; 0.14/1000 catheter days), and 15 cases of catheter colonization (12 CICCs and 3 PICCs; 2.09 episodes/1000 catheter days). Late non-infective complications were few: 14 accidental dislodgments (2.9%), 18 irreversible lumen occlusions (3.7%), and no episodes of symptomatic catheter-related thrombosis or tip migration. Conclusion: The systematic adoption of the GAVeCeLT bundles for CVAD insertion and maintenance was associated with a minimization of catheter-related complications. The strict adherence to the recommendations included in these bundles was the major determinant for clinical success.