OBJECTIVES: A novel pharmacist guided pharmacogenetic service (PGx) for patients newly started on warfarin has been implemented at the University of Illinois Hospital & Health Science System (UI-Health). Although the PGx service was found to be more effective in reducing bleeding and thrombosis related hospitalizations at 90 days post warfarin initiation compared to usual care, the cost of the genotype test and the PGx consult service warrants economic evaluation beyond 90-days of follow-up. The objective of this study was to evaluate the long-term cost-effectiveness of this novel pharmacist guided warfarin PGx service compared to usual care. METHODS: A cost-effectiveness model was developed in TreeAge Pro 2014, Williamstown, MA, USA. Patients in either the PGx or the usual care cohort followed by UI-health were included as comparators and costs and QALYs were estimated over a 5 year horizon. Warfarin related (i.e., bleeding or thrombosis) readmissions at 30 and 90 days were modeled in a decision tree. Patients in the model without a fatal event within 90 days transitioned to a Markov model with a 3-month cycle. For patients with venous thromboembolism, the Markov states included well, post intracranial hemorrhage (ICH), post thrombotic syndrome, and dead, whereas those with atrial fibrillation included well, post ICH, post stroke, post myocardial infarction and dead. Utilities, cost inputs and transition probabilities were taken from the literature and an annual 3% discount rate was used. RESULTS: At 5 years, patients managed by the PGx service had expected costs of $7412 and gains of 4.41 QALYs whereas those who received usual care had expected costs of $7926 and gains of 4.39 QALYs. CONCLUSIONS: A novel pharmacist guided warfarin pharmacogenetic service was projected to be cost-saving and to result in similar or higher QALYs by reducing hospitalizations due to warfarin related adverse events.