This study compared mood changes in 212 patients treated for hypercholesterolemia, as a function of their level of adherence to dietary recommendations. Assessments of mood (anxiety, depression, and hostility), measured by the Profile of Mood States, were obtained at baseline and 3-, 6-, and 12-month follow-up. Adherence to diet was categorized as low, medium, or high based on the Food Record Rating. Repeated-measures ANOVAs showed a significant decrease over time for anxiety, total cholesterol (TC), and low-density lipoproteins (LDL). A multiple regression was performed to determine if reductions in TC or LDL were associated with the anxiety decrease. The model for anxiety change was highly significant and included gender, baseline anxiety, number of stressful events, psychological stress, baseline level of adherence to diet, gender × adherence interaction, and change in TC × adherence interaction. In conclusion, cholesterol lowering did not negatively affect patients' moods. However, those who adhered poorly but nonetheless showed stable or reduced TC exhibited a greater decrease in anxiety.