Background <p>Coronary heart disease (CHD) is a chronic inflammatory disease carrying high morbidity and mortality. Interleukin (IL)-29 may be used as a biomarker for autoimmune diseases. This paper investigates the diagnostic value of serum IL-29 in CHD patients.</p> Methods <p>A total of 90 CHD patients (39 mild and 51 severe patients) and 90 controls were included. Serum IL-29 levels were detected by ELISA, and the diagnostic value of IL-29 in CHD was analyzed by ROC curve. According to the median value of serum IL-29 level, CHD patients were categorized into IL-29 low-level group and high-level group. The correlation between IL-29 and pathological indexes of CHD patients was analyzed by chi-square test. SYNTAX score was used to classify CHD patients into mild CHD and moderate/severe CHD. Pearson coefficient analyzed the correlation between IL-29 and CHD severity. Multivariate logistic regression analyzed the risk factors for CHD exacerbation.</p> Results <p>IL-29 serum levels were elevated in CHD patients. The AUC for CHD diagnosis by serum IL-29 was 0.789 (65.6% sensitivity and 76.7% specificity). IL-29 was correlated with BMI, PHASE score, and CRP. IL-29 serum level was positively correlated with CHD severity. The AUC for differentiating mild and moderate/severe CHD patients by IL-29 level was 0.739 (70.6% sensitivity and 66.7% specificity). IL-29 was an independent risk factor for CHD exacerbation, and each one-unit increase in IL-29 increased the risk of exacerbation in CHD patients by 1.065-fold.</p> Conclusion <p>IL-29 is highly expressed in CHD patients and has auxiliary diagnostic value for CHD.</p>