Pediatric providers can consider using the 5 P's paradigm for process improvement to optimize vaccination rates in the clinical settings: People, Processes, Pharmacy principles, Pain prevention, and Presumptive vaccine communications. Maintaining high clinical setting vaccination rates requires hiring and training the right people with vaccination details for the population being served, perfecting safe vaccine delivery processes including when and where to vaccinate, using pharmacy principles for proper vaccine storage and handling, operationalizing proper pain prevention for consistent care, and providing clear presumptive vaccine communications for success. A dedicated role of Vaccine Specialist or a clearly defined Vaccine Champion serves as the content expert of the 5 P's in the clinical setting who is critical to improving and sustaining high vaccination rates. The 5 P's Checklist for increased vaccination rates can be a tool for success in achieving and sustaining high vaccination rates in clinical settings such as ambulatory clinics, pharmacies, and school-based vaccination events. [Pediatr Ann. 2023;52(3):e89-e95.].