The effects of a pravastatin-to-simvastatin conversion program on low-density-lipoprotein (LDL) cholesterol levels were studied. Patients receiving pravastatin at a Veterans Affairs medical center were switched to simvastatin beginning in 1997. The dosage of simvastatin was based on the additional percent reduction in LDL cholesterol needed to achieve the goal specified by the National Cholesterol Education Program. The primary endpoint was the change in the percentage of patients meeting their LDL cholesterol goal at baseline and follow-up. Changes in lipid indices, the relative risk (RR) of coronary heart disease (CHD), and program costs were also evaluated. A total of 1032 patients completed the program. The mean +/- S.D. daily doses of pravastatin and simvastatin were 25.2 +/- 11.3 and 22.7 +/- 13.3 mg, respectively. Median baseline and follow-up LDL cholesterol concentrations were 116 and 99 mg/dL, respectively (p < 0.001). Overall, 44% of the patients met their LDL cholesterol goal while taking pravastatin, compared with 69% after conversion to simvastatin (p < 0.001). The predicted mean RR of a future CHD event (based on changes in serum lipids) was 0.87 (95% confidence interval, 0.83-0.91) four years after conversion. The total cost of the program was $40,644 in the first year, and there was a net saving thereafter. Therapeutic interchange between pravastatin and simvastatin increased the number of patients meeting their LDL cholesterol goal.