The association between adherence to medical recommendations and health outcomes (physical, role, and social functioning, energy/fatigue, pain, emotional well-being, general health perceptions, diastolic blood pressure, and glycohemoglobin) was examined in a 4-year longitudinal, observational study of 2125 adult patients with chronic medical conditions (hypertension, diabetes, recent myocardial infarction, congestive heart failure) and/or depression. Change score models were evaluated, controlling for disease and comorbidity. Patient adherence was associated minimally with improvement in health outcomes in this study. Only 11 of 132 comparisons showed statistically significant positive effects of adherence on health outcomes. We conclude that the relationship between adherence and health outcomes is much more complex than has often been assumed.