Although the association of serum lipid levels with the risk of atherosclerosis is well-recognized, the relation between these levels and restenosis after coronary angioplasty is uncertain. This study examines 186 patients enrolled in a trial of fish oil for prevention of restenosis. Fasting lipid levels (cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides) were measured before angioplasty, and in 90 patients repeated at 6-month follow-up. Fifty-nine patients (32%) developed clinical restenosis confirmed by angiography. Patients who went on to develop restenosis underwent multivessel angioplasty (p less than 0.05) and were more likely to be on lipid-lowering therapy at baseline (27 vs 13%; p less than 0.05). In addition, they had higher baseline cholesterol/HDL ratios (6.5 +/- 2.2 vs 5.9 +/- 2.0; p less than 0.05) and triglyceride levels (233 +/- 210 vs 183 +/- 112 mg/dl; p less than 0.05). Multiple logistic regression analysis confirmed cholesterol/HDL ratios at baseline (p = 0.021) and follow-up (p = 0.0008) to be independent predictors of risk for restenosis. Using these data, regression lines have been developed that predict risk of restenosis based on type of procedure and on lipid values. These results suggest that serum lipid levels may be associated with the risk of clinical restenosis after coronary angioplasty.