There is growing clinical interest in liver transaminases as novel biomarkers of cardiovascular risk. We investigated the possible association of serum liver transaminase activity with the presence and angiographic severity of premature coronary artery disease (CAD). A cross-sectional study was conducted on 187 younger patients (females < 55 years and males < 45 years) who underwent coronary angiography and had serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and high-sensitivity C-reactive protein (hsCRP) measured. Evaluation of coronary stenosis was by Gensini score. Both ALT and AST were significantly correlated with the presence of CAD in univariate and multivariate analyses. Both ALT and AST were also significantly correlated with Gensini score even after adjustment for potential confounders. Serum ALT and AST levels are independently positively associated with the risk and severity of premature CAD, suggesting that these enzymes could serve as surrogate markers for cardiovascular risk in this specific group of patients.