OBJECTIVES: One of the major challenges with vaccination is achieving high compliance for all required doses of vaccine. Despite strong clinical evidence, policy and marketing efforts, the compliance for several vaccination programs remains low. Often patients fail to receive the required subsequent doses of the vaccine. We developed and tested a persistency program to test its effectiveness in improving patient compliance with vaccines. METHODS: The current compliance rates were reviewed using published literature. Information on standard of care was collected from prescribers and treatment centers. 10,000 prescribers in a zip code level referral network were enrolled. Support system was set up to send telephonic and letter reminders to 90,000 patients for upcoming appointments. Providers shared reports on patient appointments allowing for Just-In-Time ordering. We developed billing guides for practices identifying commonly used codes. The duration of this study was 1 year. The data for number of missed doses and vaccinations were collected for all patients. RESULTS: There was a significant increase in compliance with patients that were sent reminders as part of this persistency program. The 2nd injection compliance was 61% and 3rd injection compliance was 42%, which is more than 40%-50% improvement over the standard of care. As clinically expected higher compliance led to improved and stable titer level in all patients. During feedback surveys, both patients and providers reported the benefit of having a support staff that was trained in clinical and reimbursement aspects. CONCLUSIONS: Persistency programs can significantly improve patient compliance by providing support, training and reminders to patients. Such programs can improve compliance, achieve better outcomes, save longer term costs for payers and collect real-world data.