BACKGROUND: To assess long-term effectiveness of a multifactorial intervention at the work-site on serum cholesterol levels. METHODS: Individualized face-to-face counseling was given to 1,555 employees (76.7% male; mean age = 42.3 years) by occupational physicians at four work-sites. After 3 years, a blinded assessment of the adequacy of the intervention was done. Implementation of the intended intervention by physicians was assessed as adequate in two work-sites (927 employees) and inadequate in the other two (628 employees). Observed changes in serum cholesterol were analyzed in the followed-up individuals. Follow-up rates at each work-site were 78.6% and 44.5% for the adequate intervention, and 85.5% and 60.4% for the inadequate intervention. Changes in serum cholesterol were controlled for potential confounding factors (pre-test levels of risk factors, age, sex, body mass index, educational level, marital status, physical activity and alcohol consumption) by multiple linear regression procedures. RESULTS: When the intervention was adequately performed, serum cholesterol was significantly lowered with a mean reduction of 14.3 mg/dl (95% C.I.: 11.0 to 17.6) in those employees with baseline levels > or = 200 mg/dl. CONCLUSIONS: Adequacy of implementation of work-site programs determines their long-term effectiveness in reducing mean serum cholesterol levels.