BackgroundChronic diseases are the leading cause of disability and death in the United States. Clinical pharmacists have been shown to optimize health outcomes and reduce health care expenditures in patients with chronic diseases through improving medication adherence. ObjectiveThe primary objective of this study was to evaluate a pharmacist-led, artificial intelligence (AI)–supported medication adherence program on medication adherence, select disease control measures, and health care expenditures. MethodsThis was a multicenter, retrospective, quasi-experimental evaluation from January 2019 to December 2019 (preimplementation) and January 2021 to December 2021 (postimplementation). This pharmacy-driven service focuses on improving medication adherence and patient outcomes through AI-supported analytics, individual patient case review, and pharmacist-led individual patient outreach. The primary end point was to determine whether implementation improved medication adherence in 3 medication-related measures: medication adherence for hypertension (MAH), medication adherence for cholesterol (MAC), and medication adherence for diabetes (MAD). Secondary outcomes were to evaluate reductions in select chronic diseases control measures and cost savings of this service after implementation of this service. ResultsThis medication adherence service was deployed across 10,477 patients: 60.6% of patients were in at least 1 medication-related measure, generating 2762 actionable medication adherence gaps. After the implementation of this pharmacist-led program, medication adherence improved in all 3 disease state measures (MAH 5.9% improvement, MAC 7.9% improvement, MAD, 6.4% improvement), and Medicare Star ratings also improved. The percentage of patients with diabetes who reached their A1c goal also increased (75.5%-81.7%). Furthermore, reductions in overall health care expenditures were seen per member per month in patients who were adherent in comparison with those who were nonadherent (hypertension 31% cost savings, hyperlipidemia 25% cost savings, diabetes 32% cost savings). ConclusionThis clinical pharmacist–driven service leveraged technology and patient connection to increase medication adherence in patients with chronic disease states and led to improvement in select disease control measures and substantial health care cost savings.