To examine the potential adverse psychological effects of screening for hypercholesterolemia, 287 men working at a motor-car assembly or steel-making plant who were ultimately diagnosed as having hypercholesterolemia and 236 randomly selected normal cholesterol controls from the same plants completed psychological questionnaires at the initial screen and 1-year later. At baseline and before diagnosis, hypercholesterolemic men scored higher on mental health and lower on negative affect than controls (p values < 0.05). One year later no adverse changes on the psychological measures were found irrespective of the type of follow-up care that they were randomly assigned to receive. Surprisingly only about half of the hypercholesterolemic men believed they had hypercholesterolemia at follow-up despite being told otherwise. Baseline scores of those who did not accept the label (n = 122) [classified as deniers] were higher on measures of positive affect and lower on measures of negative effect than those of hypercholesterolemic men who accepted the disease label (n = 73) (p values < 0.05). Moreover they held more negative attitudes towards dietary change at baseline (p < 0.03), made fewer dietary changes (p values < 0.05), and had a lesser change in total cholesterol. We conclude that a hypercholesterolemia detection and treatment program conducted in a working adult population had no adverse psychological consequences. It did, however, reveal a large subset of hypercholesterolemic men who did not accept the label despite being told they had this problem. Denial was a significant barrier to health behaviour change and may represent a maladaptive coping style for men at risk of cardiovascular disease. High cholesterol appears to be associated with better mental health and those who deny having hypercholesterolemia have the best mental health. The multifarious relationship between cholesterol, mental health, and denial deserves further study.