Objective: High-quality patient-clinician communication is associated with better medication adherence, but the specific language components associated with adherence are poorly understood. We examined how patient and clinician language may influence adherence.Methods: We audio-recorded primary care encounters from 63 patients newly diagnosed with depression and prescribed an antidepressant medication. We rated clinicians' language (motivational interviewing-adherent statements [MIAs], reflections, and global ratings of empathy and "motivational interviewing spirit") along with patients' "change talk" (CT) demonstrating motivation to take medication. Filling a first prescription and an estimate of overall adherence, the proportion of >180 days covered (PDC) (primary outcome), were measured based on pharmacy records.Results: Fifty-six patients (88.8%) filled an initial prescription, and mean (standard deviation) PDC across all subjects was 45.2% (33.6%). MIAs, complex reflections, and empathy were associated with more CT (for all: r s >0.27; P < .05). Two or more and 0 or 1 CT statements were associated with 63.0% and 36.6% PDC, respectively. Empathy, motivational interviewing spirit, and CT were associated with filling the first prescription (for all: r s >0.25; P < .05). In an adjusted analysis, empathy (t ؍ 2.3; P ؍ .027) and >2 CT statements (t ؍ 2.3; P ؍ .024) were associated with higher PDC. Nonadherence to antidepressant medication is one of a few potentially modifiable predictors of a poor clinical outcome for people with depression, 1-3 and up to 50% of adults treated for depression in primary care experience clinically significant nonadherence due to side effects, delay in symptom relief, perceived harm of antidepressant medications, and other factors. 4,5 Up to 10% experience primary nonadherence due to not picking up the initial prescription. 6,7 Despite decades of research, there is currently a lack of knowledge about simple, effective interventions to improve medication adherence, and a Cochrane review concluded that most adherence interventions failed to achieve enduring medication adherence or improve patient outcomes.8 Meta-analytical evidence identifies the patient-clinician communication process as a critical and modifiable determinant of subsequent antidepressant adherence, and novel interventions targeting aspects of communication hold promise for positive effects. 9 -11 Yet which aspects of the clinician's or patient's communication are specifically associated with better or worse adherence are unclear.Researchers in the field of motivational interviewing (MI), a patient-centered style of communication intended to help patients resolve ambivalence and work toward improving a targeted maladaptive behavior, 12 have developed instru-