Recent studies demonstrate important roles for inflammation in development of atherosclerosis with current attention focusing on interactions of inflammation with traditional lipoprotein risk factors. Since the nature of such relationships is largely unknown, we sought to investigate interactions of inflammation with hyperlipidemia in generating cardiovascular risk in a way that would allow recognition of such interactions whether anticipated or not. Thus, we searched for subgroups at high risk for recurrent coronary events in 767 non-diabetic postinfarction patients using an exploratory three-dimensional graphical screening technique with previously established factor analysis-derived inflammatory and lipoprotein-related factors. Results indicated a high-risk patient subgroup defined by factor interaction that was best characterized clinically by high levels of C-reactive protein (CRP) and total cholesterol. Kaplan-Meier and Cox multivariate analysis confirmed high-risk. Additionally, within-subgroup risk related to metabolic, inflammatory, and thrombogenic blood markers was assessed using Cox analysis with results showing only elevated HDL as a significant and independent predictor of risk with hazard ratio, 2.24 (95% CI; 1.12, 4.49; p = 0.023). We conclude that in non-diabetic postinfarction patients, elevated HDL is predictive of risk of recurrent coronary events within a subgroup of patients characterized by simultaneous elevations in serum CRP and total cholesterol.