Although serum aminotransferase levels are frequently measured for preoperative evaluation, their prognostic value to postoperative outcomes remain unclear. This study aimed to investigate the relationship between preoperative serum aminotransferase levels and postoperative 90-day mortality in patients undergoing cardiovascular surgery. We included adult patients (n=6264) who underwent cardiovascular surgery between January 2010 and December 2016 at a tertiary academic hospital. Preoperative serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and De Ritis ratio (defined as AST/ALT) were categorized into three groups: low (≤20th percentile), middle (20th–80th percentile), and high (>80th percentile). Of the 6264 patients enrolled (40.4% women; median age, 62 years), 183 (2.9%) died within 90 days postoperatively. Multivariable-adjusted analyses revealed low ALT (hazard ratio 1.58, 95% confidence interval, 1.14–2.18) and high De Ritis ratio (hazard ratio 1.59, 95% confidence interval, 1.15–2.20) were independent predictors of postoperative mortality, but AST did not have a statistically significant association. The association of low ALT and high De Ritis ratio with 90-day mortality was more pronounced in patients older than 60 years (P-values for interaction <0.05). Therefore, preoperative serum aminotransferase levels may be a valuable prognostic marker in patients with cardiovascular surgery, particularly in the elderly.