This cross-sectional study investigated the association of lipoprotein(a) [Lp(a)] levels as an atherosclerosis predictor and their relationship to the severity of coronary artery disease (CAD). Methods: 360 consecutive patients at Sanjay Gandhi Postgraduate Institute of Medical Sciences and King George's Medical University hospitals, Lucknow, North India, with chest pains, CAD symptoms and on lipid-lowering therapy were enrolled between June 2009 and October 2011. Before coronary artery angiography (CAG), a fasting blood sample was assessed for lipid and Lp(a) levels. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score was calculated according to the CAG results. Patients were divided into 3 groups based on CAD severity and SYNTAX scores. Results: Angiography revealed CAD in 270 patients. Lp(a) levels were higher in CAD compared to non-CAD patients (48.7 ± 23.8 mg/dl versus 18.9 ± 11.1 mg/dl [P <0.0001]). The levels of Lp(a)were lower in single than in double and triple vessels (39.3 ± 18.4 mg/dl versus 58.0 ± 23.0 mg/dl, and 69.2 ± 24.1 mg/dl, [P <0.05]). Lp(a) levels were significantly higher in severe CAD with SYNTAX score >30 (88.0±24.0 mg/dl). Lp(a) levels correlated significantly with SYNTAX scores (r = 0.70, P <0.0001). Conclusion: In this study, Lp(a) levels were positively associated with a patient's SYNTAX score in diseased vessels. Furthermore, an elevated Lp(a) level was a causal, independent risk factor of CAD. Lowering Lp(a) levels would reduce CAD in primary and secondary prevention settings. There is an urgent need to define more precisely which patients to treat and which to target for earlier interventions.