High-sensitivity C-reactive protein (hs-CRP) plays an important role in hypoalbuminemia as a representative of inflammation, which is closely associated with poor prognosis among patients with coronary artery disease (CAD). The present study aimed to evaluate the independent and joint effects of high hs-CRP levels and hypoalbuminemia on long-term mortality among CAD patients.A total of 1449 CAD patients were included from a prospective, multicenter, observational cohort study (REICIN, NCT01402232) of patients referred for coronary angiography (CAG). The primary endpoint was long-term all-cause death.During a median follow-up of 2.9 (2.0-3.0) years, a total of 107 (7.4%) patients died. The long-term mortality was higher among CAD patients with high hs-CRP levels (> 3 mg/L) than those with the low hs-CRP levels (≤ 3 mg/L; 10.7% versus 4.1%; hazard ratio [HR] 2.49; 95% confidence interval [CI] 1.48-4.17). Similarly, CAD patients with hypoalbuminemia had higher mortality than those without hypoalbuminemia (12.2% versus 4.9%; HR 1.93; 95% CI 1.20-3.08). When hs-CRP and albumin were combined, CAD patients with high hs-CRP levels (> 3 mg/L) and with hypoalbuminemia were at the highest risk of death compared with their reference group (hs-CRP ≤ 3 mg/L and albumin > 35 g/L; HR 3.79; 95% CI 1.91-7.52).High hs-CRP levels and hypoalbuminemia were independently and jointly associated with long-term mortality among CAD patients. Patients with high hs-CRP levels and hypoalbuminemia had the highest risk of long-term mortality compared with other groups.© 2021. The Author(s).