Background Low muscle mass has been associated with poor prognosis in certain chronic diseases, but its clinical significance in patients with coronary artery disease is unclear. We assessed the clinical significance of 2 easily measured surrogate markers of low muscle mass: the ratio of serum creatinine to serum cystatin C (Scr/Scys), and the ratio of estimated glomerular filtration rate by Scys to Scr (eGFRcys/eGFRcr). Methods and Results Patients with coronary artery disease undergoing percutaneous coronary intervention were prospectively enrolled from a single tertiary center, and Scr and Scys levels were simultaneously measured at admission. Best cut-off values for Scr/Scys and eGFRcys/eGFRcr to discriminate 3-year mortality were determined; 1.0 for men and 0.8 for women in Scr/Scys, and 1.1 for men and 1.0 for women in eGFRcys/eGFRcr. The prognostic values on 3-year mortality and the additive values of 2 markers on the predictive model were compared. In 1928 patients enrolled (mean age 65.2±9.9 years, 70.8% men), the risk of 3-year mortality increased proportionally according to the decrease of the surrogate markers. Both Scr/Scys- and eGFRcys/eGFRcr-based low muscle mass groups showed significantly higher risk of death, after adjusting for possible confounders. They also increased predictive power of the mortality prediction model. Low Scr/Scys values were associated with high mortality rate in patients who were ≥65 years, nonobese, male, had renal dysfunction at baseline, and presented with acute myocardial infarction. Conclusions Serum surrogate markers of muscle mass, Scr/Scys, and eGFRcys/eGFRcr may have clinical significance for detecting patients with coronary artery disease at high risk for long-term mortality.