The efficacy of interventions to improve adherence may be increased by targeting interventions to patients that demonstrate both poor adherence and poor disease control, tailoring interventions to individual patient needs, and touching larger and more representative patient populations and care settings. The Study of a Tele-pharmacy Intervention for Chronic diseases to Improve Treatment adherence (STIC2IT) trial enrolled 4,076 patients to evaluate the impact of a novel tele-pharmacist intervention on adherence to maintenance medications. The study also assesses the cost-effectiveness of the tele-pharmacist intervention and uses insurance claims data to validate the use of novel methods to assess medication adherence.