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Purpose: To identify parsimonious models for changes in depression in spouses of post myocardial infarction (MI) patients over 2 years based on the biopsychosocial model. Methods: A total of 442 community living patients who had experienced an MI and their spouses were included for analysis. Patients and spouses completed psychosocial assessments at baseline, 1 year, and 2 years after enrollment in the Patients' and Families' Psychological Response to Home Automated External Defibrillator Trial. Linear mixed models were used for testing hypotheses. Results: A total of 15.2% (baseline), 11.5% (1-year follow up), and 8.1% (2-year follow up) of spouses were depressed. Spouse biological factors did not influence changes in depression. Among all spouses, two groups of spouses showed increased depression over time: spouses with lower baseline depression scores (p