To confirm whether growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity 2 (sST2) are indicators of pulmonary hypertension in acute exacerbation of chronic obstructive pulmonary disease (AECOPD-PH).All patients admitted to the hospital with AECOPD between July 2020 and October 2021 were enrolled. The patients were then categorized into AECOPD and AECOPD-PH groups according to PH probability, and the differences in GDF-15 and sST2 serum levels in the AECOPD and AECOPD-PH groups were compared. Correlation analysis was carried out to explore the association between GDF-15 and sST2 serum levels and the length of hospital stay of patients with AECOPD-PH. Receiver operating characteristic curve analysis was used to assess the clinical significance of GDF-15 and sST2 in predicting patients with AECOPD-PH.Included in this study were 126 patients with AECOPD, including 69 with AECOPD and 57 with AECOPD-PH. The serum levels of GDF-15 and sST2 in the AECOPD-PH group were significantly higher than those in the AECOPD group (P < 0.05). There was no significant correlation between the length of hospital stay in AECOPD-PH patients and GDF-15 and sST2 serum levels (P > 0.05). The area under the curves of GDF-15, sST2, and GDF-15 + sST2 for predicting AECOPD-PH and AECOPD-PH patients with poor prognosis were >0.60 and 0.70, respectively. The optimal cutoff values of GDF-15 and sST2 for predicting AECOPD-PH were 1125.33 pg/mL and 80.68 ng/mL and 1309.72 pg/mL and 59.10 ng/mL for predicting AECOPD-PH patients with poor prognosis, respectively.GDF-15 and sST2 levels may be useful in the prediction of AECOPD-PH.© 2023 Lv et al.