Background: Recent studies have suggested soluble tumor necrotizing factor-like weak inducer of apoptosis (sTWEAK) and sCD163 may be a potential cardiovascular biomarker. We aimed to evaluate sTWEAK and sCD163 levels and predictive values in patients with chronic coronary artery disease (CAD) and acute coronary syndrome (ACS). Methods: Two hundred fourteen angiography-made patients were enrolled in the study and divided into 3 groups: 30 controls with normal angiograms, 99 patients with ACS, 85 patients with chronic CAD. sTWEAK, sCD163 and CRP levels were measured. Receivers operating characteristic (ROC) curve analysis were performed to determine the predictive values of sTWEAK and sCD163 levels and the sCD163/sTWEAK ratio. Gensini scores were used to assess severity of CAD. Results: sTWEAK levels in chronic CAD and ACS patients were lower compared to the control group (P<0.0001). sCD163 levels (P<0.0001) and the sCD163/sTWEAK ratio (P<0.0001) were higher in the ACS patients compared to the control and chronic CAD patients. ROC analysis revealed low sTWEAK level and high sCD163/sTWEAK ratio predicted chronic CAD, and low sTWEAK, high sCD163, CRP levels and sCD163/sTWEAK ratio predicted ACS. According to ROC analyses, significance of sTWEAK levels for chronic CAD was more marked compared to ACS (P<0.0001 vs P=0.001) and significance of sCD163/sTWEAK ratio was greater than sTWEAK for ACS (P<0.0001 vs P=0.001). These parameters didn't correlate with severity of disease, obtained gensini scoring, in chronic CAD. Conclusions: It was concluded thats TWEAK level may be a diagnostic marker of especially chronic CAD, sCD163 level of ACS, and the sCD163/sTWEAK ratio of both chronic CAD and ACS.