Background Poor medication adherence is common; however, few mechanisms exist in clinical practice to monitor how patients take medications in outpatient settings. Objective This study aimed to pilot test the Electronic Medication Complete Communication (EMC2) strategy, a low-cost, sustainable approach that uses functionalities within the electronic health record to promote outpatient medication adherence and safety. Methods The EMC2 strategy was implemented in 2 academic practices for 14 higher-risk diabetes medications. The strategy included: (1) clinical decision support alerts to prompt provider counseling on medication risks, (2) low-literacy medication summaries for patients, (3) a portal-based questionnaire to monitor outpatient medication use, and (4) clinical outreach for identified concerns. We recruited adult patients with diabetes who were prescribed a higher-risk diabetes medication. Participants completed baseline and 2-week interviews to assess receipt of, and satisfaction with, intervention components. Results A total of 100 patients were enrolled; 90 completed the 2-week interview. Patients were racially diverse, 30.0% (30/100) had a high school education or less, and 40.0% (40/100) had limited literacy skills. About a quarter (28/100) did not have a portal account; socioeconomic disparities were noted in account ownership by income and education. Among patients with a portal account, 58% (42/72) completed the questionnaire; 21 of the 42 patients reported concerns warranting clinical follow-up. Of these, 17 were contacted by the clinic or had their issue resolved within 24 hours. Most patients (33/38, 89%) who completed the portal questionnaire and follow-up interview reported high levels of satisfaction (score of 8 or greater on a scale of 1-10). Conclusions Findings suggest that the EMC2 strategy can be reliably implemented and delivered to patients, with high levels of satisfaction. Disparities in portal use may restrict intervention reach. Although the EMC2 strategy can be implemented with minimal impact on clinic workflow, future trials are needed to evaluate its effectiveness to promote adherence and safety.