Background Elevated lipoprotein(a) (Lp[a]) and low-density lipoprotein (LDL) cholesterol are important inheritable risk factors for premature coronary artery disease (CAD). Lp(a) mediates cardiovascular risk through prothrombotic, proinflammatory, and proatherogenic properties. The association of Lp(a) and LDL cholesterol with angiographic disease severity and complexity in patients with premature CAD has yet to be established. Objective To investigate the relationship of Lp(a) and LDL cholesterol with the severity and complexity of coronary artery lesions using the SYNergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery (SYNTAX) and Gensini scores, in patients with premature CAD. Methods Plasma Lp(a) levels were consecutively measured by an automated latex-enhanced immunoassay in 147 patients with premature coronary events (aged <60 years). Elevated Lp(a) was defined as >0.5 g/L, and elevated LDL cholesterol as an untreated LDL cholesterol of >5.0 mmol/L (>193 mg/dL). Demographical, biochemical, and clinical data were retrospectively collected from medical records. SYNTAX and Gensini scores were independently assessed by 2 investigators. Results Patients were subdivided into tertiles using SYNTAX scores. The proportion of patients with elevated Lp(a) and elevated LDL cholesterol were significantly higher in patients with higher SYNTAX and Gensini scores (P < .05). In multivariate analysis (adjusting for age, diabetes, hypertension, and previous coronary event), elevated Lp(a) and elevated LDL cholesterol remained significant, independent predictors of higher SYNTAX and Gensini scores (P < .05). Patients with both elevated Lp(a) and elevated LDL cholesterol constituted most of the patients in the highest SYNTAX tertile, while patients with nonelevated Lp(a) and nonelevated LDL cholesterol were predominantly in the lowest SYNTAX tertile (P < .05). Conclusion In patients with premature CAD, elevated Lp(a) and LDL cholesterol (in a range consistent with familial hypercholesterolemia) were significant, independent predictors of the severity of CAD. Both lipid disorders should be routinely screened for in younger patients presenting to the coronary care unit.