Aim To investigate the clinical significance of serum growth differentiation factor 15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI) changes at different time and its relationship with short-term prognosis in patients with cardiac arrest cardiopulmonary resuscitation. Methods The serum levels of GDF-15 were detected in 102 CPR patients at instant time, 12 h, 24-48 h after CPR. According to the rise time of serum GDF-15, the patients were divided into 3 groups:(1)A group:at instant time, 12 h, 24-48 h after CPR, GDF-15 levels had been less than 1200 ng/L; (2)B group:at 12 h and 24-48 h after CPR, GDF-15 levels were increased, and more than 1200 ng/L; (3)C group:at instant time, 12 h after CPR, GDF-15 levels were increased, but GDF-15 level at 24-48 h was lower than that at 12 h. At each time point, the serum levels of NT-proBNP and cTnI, left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were detected at the same time in 3 groups. The death situation of 3 groups was followed up for 6 months after CPR. Results GDF-15 had an interaction with NT-proBNP and cTnI (P＝0.001). LVEDD and LVEF were changed with the changes of GDF-15, NT-proBNP and cTnI levels. The mortality rates of patients in GDF-15, NT-proBNP and cTnI high level groups were higher than those in GDF-15, NT-proBNP and cTnI low level groups (P＜0.05). Survival analysis results showed that the 6 month survival rate of A group was higher than that of B group (χ²＝12.738, P＝0.001), the 6 month survival rate of B group was lower than that of C group (χ²＝7.253, P＝0.009), and there was no significant difference in 6 month survival rate between A group and C group (χ²＝2.240, P＝0.097). Conclusion The serum levels of GDF-15, NT-proBNP and cTnI are good indicators for predicting the short-term prognosis of CPR patients, and the significance of combined detection is even higher.