We will assess the effectiveness and fidelity of a primary care-based, technology-enabled strategy to improve patient-provider communication about prescribed, higher-risk medications to ensure safe use. Research has repeatedly demonstrated that individuals lack essential information on how to safely take prescribed (Rx) medications. Knowledge deficits are greatest for information pertaining to risks and warnings. Inadequate patient knowledge has been cited as a root cause of unintentional misuse, which can lead to serious adverse drug events (ADEs). This is not surprising, as neither physicians nor pharmacists may routinely counsel patients on medication risks and safe use. Instead, patients depend on product labeling, which is limited in clarity and effectiveness. Our team has found that even when evidence-based, health literacy best practices are employed to these written tools, the elderly and those with low literacy continue to be inadequately informed and are therefore at greater risk for medication errors and/or suboptimal treatment. A risk communication and surveillance strategy is needed in primary care to ensure that patients are adequately informed about medication risks and are taking prescribed regimens safely. This is most salient for medications the Food & Drug Administration (FDA) has deemed to possess serious public health concerns, warranting a Medication Guide and/or Risk Evaluation and Mitigation Strategy (REMS). To our knowledge, no such strategy exists to support and monitor outpatient Rx use in a cost-sustainable manner. We devised an Electronic health record-based Medication Complete Communication (EMC2) Strategy that leverages electronic health record (EHR) and interactive voice response (IVR) technologies to: 1) prompt and guide provider counseling, 2) automate the delivery of Medication Guides at prescribing, 3) follow patients post-visit to confirm Rx understanding and use, and 4) deliver a care alert back to providers to inform them of any potential harms. The proposed study targets 33 higher-risk medications commonly prescribed by clinicians at federally qualified health centers in Chicago. We will conduct a 2-arm, multi-site, physician-clustered randomized trial to: 1) Test the effectiveness of the EMC2 Strategy to improve patient understanding and use of higher-risk medications, and to increase the detection of medication errors and ADEs in primary care 2) Assess whether the EMC2 Strategy can reduce disparities in understanding and safe Rx use by patient literacy level, English proficiency, and age 3) Evaluate the effectiveness and fidelity of the EMC2 Strategy to promote provider counseling, deliver patient Rx information, monitor understanding and use, and inform providers of harms 4) Explore patient, provider, and system barriers to the implementation and effectiveness of the EMC2 Strategy 5) Determine the cost of delivering the EMC2 strategy in primary care from a health system perspective