Pharmacogenomics can only be effectively and ethically implemented into routine care if patients are informed about the results of their pharmacogenomic testing, so they can understand changes made to their medications and inform future providers about relevant findings. There are significant challenges to educating patients in this area. Detailed explanations may be confusing and lead to dangerous mistakes, such as stopping a medicine incorrectly without asking a healthcare provider. Materials that have been used to explain pharmacogenomic results have not been tested in diverse groups of patients and in real-life clinical situations. The ADOPT PGx trial (A Depression and Opioid Pragmatic Trial in Pharmacogenetics), funded by the Implementing Genomics in Practice (IGNITE) network of NHGRI, provides an excellent opportunity to learn more about how to adequately inform patients about their pharmacogenomic results. The trial will enroll 4500 patients with depression, chronic pain, or expected post-operative pain. Half will be randomized to undergo pharmacogenomic testing for two genes, CYP2C19 and CYP2D6, and results will be entered in the electronic medical record to guide prescription of anti-depressants and pain medicines. After completing participation, all patients will be sent a letter informing them of their pharmacogenomic test results. For the proposed supplement, we will conduct telephone interviews with 150 participants total from all sites after they receive their pharmacogenomic test results (120 with actionable results and 30 with non-actionable results). Our long- term goal is to support the ethical and effective use of pharmacogenomics in clinical medicine. The main objectives of the project are to leverage a large study to (a) explore patients’ perspectives on how they learned their pharmacogenomics results, (b) determine the usability and acceptability of a letter disclosing those results, and (c) determine patients’ objective understanding of those results. Previous studies have measured patients’ subjective understanding (how they feel about their level of knowledge) without measuring objective understanding (how they perform on a knowledge test). Our Aims are to: 1: Assess how patients learned about their pharmacogenomic test results and determine the acceptability and usability of written materials disclosing those test results. 2: Determine patients’ understanding of their results of pharmacogenomics testing and implications for future healthcare, including their intentions to discuss results with future providers. Our project is innovative because we will identify patients’ perspectives and understanding of pharmacogenomic test results in a diverse population who underwent testing in a range of real-life clinical settings. The project will produce a significant advance by providing evidence about return pharmacogenomic results that will inform development of practice guidelines and will create resources for future bioethics ...