This study aimed to implement a point-of-care ultrasound (POCUS) program into a large neonatal intensive care unit (NICU) to enhance care by improving (1) umbilical venous catheter (UVC) tip identification and (2) central placement. A POCUS program was established with core providers who received training from external and internal experts. A prospective study (n = 94) compared the accuracy of UVC identification between neonatology-performed ultrasound (NeoUS) and X-ray relative to a referent of radiology-interpreted ultrasound. Finally, an ultrasound-guided UVC insertion protocol was introduced to rescue noncentral traditionally placed catheters (n = 37). Program implementation trained six providers for a total cost of approximately $10,500 USD. NeoUS was more accurate than X-ray at identifying UVC location (81.9 vs. 60.6%) with improved sensitivity and specificity (80.0 and 84.6 vs. 52.5 and 66.7%, respectively). POCUS guidance was able to rescue 89.2% of catheters that were originally noncentral. POCUS implementation in a large NICU is feasible, affordable, and can improve quality of care. · POCUS implementation is feasible and affordable.. · POCUS is more accurate than X-ray at monitoring UVCs.. · Central UVC placement can be increased with POCUS..