Objectives We aimed to determine the predictive value of cardiopulmonary exercise testing (CPX) in the prognosis of patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Methods We conducted a retrospective study including patients who underwent CPX within 1 year of PCI between September 2012 and October 2017. Patients were followed-up until the occurrence of a major adverse cardiac event (MACE) or administrative censoring (September 2019). A Cox regression model was used to identify significant predictors of a MACE. Model performance was evaluated in terms of discrimination (C-statistic) and calibration (calibration-in-the-large). Results In total, 184 patients were included and followed-up for a median 51 months (interquartile range: 36-67 months) and 32 events occurred. Multivariable analysis revealed that body mass index and Gensini score were significant predictors of a MACE. Four CPX-related variables were found to be predictive of a MACE: premature CPX termination, peak oxygen uptake, heart rate reserve, and ventilatory equivalent for carbon dioxide slope. The final prediction model had a C-statistic of 0.92 and calibration-in-the-large 0.58%. Conclusion CPX-related parameters may have high predictive value for poor outcomes in patients with ACS who undergo PCI, indicating a need for appropriate treatment and timely management.