Oxidative stress plays a critical role in the initiation and progression of atherosclerosis. Oxidized LDL (oxLDL) is a marker of oxidative stress. We prospectively investigated whether increased serum oxLDL concentrations are associated with incident coronary heart disease (CHD.We conducted a prospective population-based case-cohort study within the MONICA/KORA Augsburg studies. Serum oxLDL concentrations were measured in 333 case individuals with incident CHD and in 1727 noncase individuals selected from a source population of 9300 middle-aged, healthy men and women. The mean (SD) follow-up time was 10.8 (4.6) years. Baseline oxLDL concentrations were higher in case individuals than in noncase individuals (P < 0.001). After adjustment for age, sex, survey, smoking status, systolic blood pressure, physical activity, diabetes, body mass index, parental history of myocardial infarction, and alcohol consumption, the hazard ratio (HR) for comparing the first and third tertiles was 1.87 (95% CI, 1.33-2.64; P < 0.001). Additional adjustment for lipid parameters, inflammatory markers, and markers of endothelial dysfunction attenuated the association (HR, 1.29; 95% CI, 0.88-1.89; P = 0.087). We observed no significant interactions between oxLDL and sex or being overweight. Increased oxLDL concentrations were associated with an increased risk for incident CHD. Nevertheless, because this effect became nonsignificant after adjustment for covariates, particularly the ratio of total cholesterol to HDL cholesterol, it may be mediated primarily by lipid parameters. Further studies are warranted to clarify this issue.