Chronic diseases are the leading cause of disability and death in the United States. Clinical pharmacists have been shown to optimize health outcomes and reduce healthcare expenditures in patients with chronic diseases through improving medication adherence. The primary objective of this study was to evaluate a pharmacist-led, artificial intelligence-supported medication adherence program on medication adherence, select disease control measures, and healthcare expenditures. This was a multicenter, retrospective, quasi-experimental evaluation from January 2019 to December 2019 (pre-implementation) and January 2021 to December 2021 (post-implementation). This pharmacy-driven service focuses on improving medication adherence and patient outcomes through artificial intelligence-supported analytics, individual patient case review, and pharmacist-led individual patient outreach. The primary endpoint was to determine if implementation improved medication adherence in three 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 following implementation of this service. This medication adherence service was deployed across 10,477 patients: 60.6% of patients were in at least one medication-related measure, generating 2,762 actionable medication adherence gaps. Following the implementation of this pharmacist-led program, medication adherence improved in all three 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% to 81.7%). Furthermore, reductions in overall healthcare expenditures were seen per member per month in patients that were adherent in comparison to those who were non-adherent (hypertension: 31% cost savings; hyperlipidemia 25% cost savings; diabetes: 32% cost savings). This 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 healthcare cost savings.