Objective To investigate the relationships between serum periostin (POSTN), signal transductor and transcriptional activator 3 (STAT3) levels and disease severity and prognosis in patients with chronic heart failure (CHF) in dilated cardiomyopathy (DCM). Methods Totally 142 patients with DCM CHF (the DCM CHF group) and 50 healthy physical examination volunteers (the control group) were selected. According to the New York Heart Association (NYHA) cardiac function classification, the patients with DCM CHF were divided into the Class I group of 16 cases, Class II group of 27 cases, Class III group of 53 cases and Class IV group of 46 cases. The patients with DCM CHF were followed up for 1 year, and were divided into the poor prognosis group (53 cases) and good prognosis group (89 cases) according to the prognosis. Enzyme-linked immunosorbent assay was used to detect serum POSTN and STAT3 in the two groups. Spearman correlation method was used to analyze the correlation between serum POSTN and STAT3 levels and NYHA cardiac function classification in patients with DCM CHF. Multifactorial Logistic regression was used to analyze the influencing factors of poor prognosis in patients with DCM CHF. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum POSTN and STAT3 levels on poor prognosis of DCM CHF patients. Results Serum POSTN and STAT3 levels were higher in the DCM CHF group than in the control group (both P<0. 05). Serum POSTN and STAT3 levels increased sequentially in the Class I, Class II, Class III, and Class IV groups (all P<0. 05). Spearman's correlation method analysis showed that serum POSTN and STAT3 levels were positively correlated with NYHA cardiac function class in patients with DCM CHF (rs =0. 814 and 0. 808, respectively; all P<0. 05). Multifactorial Logistic regression analysis showed that the older age, NYHA cardiac function class ≥ III, high N-terminal pro-B-type natriuretic peptide level, high POSTN level, and high STAT3 level were independent risk factors for poor prognosis of DCM CHF patients, and high left ventricular ejection fraction (LVEF) was an independent protective factor (all P<0. 05). ROC curve analysis showed that the area under the curve of serum POSTN combined with STAT3 in predicting poor prognosis of patients with DCM CHF was greater than that of either alone (both P<0. 05). Conclusion Serum POSTN and STAT3 levels are elevated in patients with DCM CHF, and changes in the levels of both can reflect the severity of the disease, and serum POSTN combined with STAT3 has high predictive efficacy for poor prognosis in DCM CHF patients. [ABSTRACT FROM AUTHOR]