Compared to non-Latino Whites, US racial/ethnic minority groups show higher non-adherence with outpatient antidepressant therapy, including lower retention, despite adjusting for sociodemographic and insurance covariates. Culturally salient concerns about antidepressants leading to ambivalence about treatment engagement may contribute to this discrepancy. To improve treatment adherence among depressed Latinos, we developed Motivational Pharmacotherapy, a novel approach that combines Motivational Interviewing, standard pharmacotherapy, and attention to Latino cultural concerns about antidepressants. This 12-week, open-trial, pre-post pilot study assessed the impact of Motivational Pharmacotherapy on antidepressant therapy retention, response (symptoms, functioning, and quality of life), and visit duration among N=50 first-generation Latino outpatients with Major Depressive Disorder. At study endpoint, 20% of patients discontinued treatment, with a mean therapy duration of 74.2 out of 84 days. Patients’ symptoms, psychosocial functioning, and quality of life improved significantly. Mean visit length was 36.7 minutes for visit 1 and 24.3 minutes for subsequent visits, compatible with use in community clinics. Responder and remitter rates were 82% and 68%. Compared to published Latino proportions of non-retention (32-53%) and previous studies at our clinic with similar samples and medications (36-46%), Motivational Pharmacotherapy appears to improve Latino retention in antidepressant therapy, and should be investigated further in controlled designs.