The report aims to review the literature and describe the methods used for retention of patients in a clinical study. The Enhanced Recovery in Coronary Heart Disease (ENRICHD) trial was a multicenter, randomized clinical trial designed to evaluate the effects of a psychosocial intervention on cardiovascular morbidity and mortality. A total of 2481 patients met the criteria for depression, low social support, or both after a myocardial infarction and needed to be followed. Follow-up evaluation consisted of telephone interviews 3, 9, 12, 24, 36, and 48 months after enrollment and clinic visits scheduled at 6, 18, 30, 42, and 54 months. Creative strategies used to achieve optimum retention of this complex patient population over a long follow-up period are presented. Strategies to enhance adherence throughout the course of the trial required adequate tracking of patients to ensure minimum dropout, follow-up evaluation optimized through multiple methods of contact to guarantee completeness of data collection; and development of procedures to address the needs of patients at risk for dropout. Patients in the group that completed the study participated for a mean of 28.3 months, and those lost to follow-up evaluation participated for a mean of 19 months. Retention was not substantially different by gender or minority status. The results of this project can assist investigators in planning studies that require patient follow-up evaluation, and can provide clinicians with specific strategies for maximizing retention-to-treatment recommendations. As a result of the retention strategies described in this report, 93.02% of the patients completed their study participation or died. This is a very high retention rate given the complexity of the study sample, protocol, and required duration of follow-up evaluation.