Purpose The purpose of this study is to assess factors related to diabetes medication nonadherence in a sample of predominantly Spanish-speaking Mexican-origin adults residing along the US-Mexico border. As part of a randomized controlled trial, 302 patients randomly sampled from a clinic roster completed a baseline interview. Medication nonadherence was assessed with the Morisky Medication Adherence Scale. Consistent with the framework proposed by Venturini et al, four factors were examined: patient-related attributes, drug regimen characteristics and complexity, health status, and patient-provider interaction characteristics. Sixty percent of the patients were classified as nonadherent. Men, those who engaged in diabetes control behaviors less frequently, and individuals with depression were more likely to be classified as nonadherent. Among those who were Spanish-dominant, education and self-rated health also were significantly and negatively related to medication adherence; patients with a high school education or greater and those who more positively rated their health were more likely to be classified as nonadherent compared to those with less than a high school education and those who rated their health as poor. Results reflect potentially higher medication nonadherence rates for Latinos with type 2 diabetes living in rural communities along the US-Mexico border. Additionally, this study supports the need to address strategies to support medication adherence, including addressing depression, for diabetes control. Strategies to promote adherence among Latino men are sorely needed, as are strategies to address forgetfulness and carelessness regarding diabetes medicine taking. © 2012, SAGE Publications. All rights reserved.