OBJECTIVES: The aim of this study was to analyse the cost-effectiveness of consecutive supplementing of the Framingham scoring (FRS) algorithm for coronary artery disease (CAD) risk assessment with apolipoproteins B and A-I (apoA-I and apoB), the apo (a) phenotype, lipoprotein (a), and high sensitivity C-reactive protein (hs-CRP). The perspective of the analysis is the clinical laboratory setting. METHODS: The study is prospective diagnosing of 221 CAD patients and 289 controls. First line testing followed the guidelines for risk assessment based on FRS. Risk factors included in the FRS are: age, total cholesterol, high density cholesterol, systolic blood pressure, treatment for hypertension and cigarette smoking. FRS classifies individuals into those with 10-year risk for CAD of >20% event risk (high risk group), 10-20% event risk (intermediate risk group) and <10% event risk (low risk group). The FRS algorithm was supplemented with apolipoproteins, lipoproteins and hs-CRP and the effectiveness was measured in number needed to diagnose (NND). Total cost of diagnostic procedure was calculated on the basis of the consumed resources for diagnostic tests, labor time, and consumables. To evaluate the additional number needed to be diagnosed for successful CAD risk establishment was performed and incremental cost-effectiveness analysis. RESULTS: A diagnostic strategy employing FRS followed by apoA-I had lowest cost per additionally successfully diagnoses patient than the same strategy followed by hs-CRP in the low (2.63 vs. 24.47 euros) and intermediate risk groups (2.93 vs. 122.86 euros). In the high-risk group the diagnostic strategy employing apo A-I was the cost-effective strategy. It had a lower ICER (-9.14 euros) than the strategy employing hs-CRP (7.16 euros). CONCLUSION: Cost-effectiveness analysis of different diagnostic markers results in improved identification of at-risk patients at a lower health cost for society. In the clinical laboratory setting it is sufficient to determine apoA-I concentration in addition to FRS for CAD risk assessment.