Abstract Background Percutaneous coronary intervention (PCI) has demonstrated a significant positive prognostic impact on outcomes in patients with Non-ST-elevation myocardial infarction (NSTEMI). However, PCI is associated with an increased risk of periprocedural complications, among which periprocedural myocardial infarction (PMI). Although risk factors of periprocedural events are only well established in patients undergoing PCI for chronic coronary syndrome with normal baseline cardiac troponin (cTn) levels, evidence on predictors of additional post-PCI myocardial infarction in patients with acute coronary syndrome who present elevated cTn levels at baseline (pre-PCI) is missing. Purpose To identify the predictors of PMI in patients affected by NSTEMI undergoing PCI. Methods We prospectively evaluated all NSTEMI patients admitted to our coronary care unit from 2017 to 2022 who underwent PCI. NSTEMI patients were managed according to the current European guidelines criteria. The diagnosis of PMI (type 4a myocardial infarction) was based on the Fourth Universal Definition of Myocardial Infarction. We only enrolled patients with stable (≤ 20% variation) or falling pre-procedure baseline cTn values. A multivariable logistic regression analysis was performed to investigate the factors independently associated with the occurrence of PMI after PCI. For the analysis, we selected the main known predictors of PMI after elective PCI, specifically age, serum creatinine, GRACE score > 140, multivessel disease, coronary bifurcation PCI, left main or proximal left anterior descending PCI, multivessel PCI and stent length ≥ 60 mm. Results The final court of the study included 1412 patients. PMI was recognized in 240 patients (17.0%). Although the patients who developed PMI had a higher risk profile as documented by a higher mean age, a higher complexity of atherosclerotic disease, and thus a significant technical difficulty of PCI compared to other patients, according to the multivariable model, only age [OR: 1.02 (95% CI: 1.01-1.04); p=0.006], coronary bifurcation PCI [OR: 3.71 (95% CI: 2.70-5.10); p<0.001], and stent length ≥ 60 mm [OR: 1.87 (95% CI: 1.30-2.68); p=0.001] were independent predictors of PMI. Interestingly, despite previous studies have demonstrated a predictive role of procedural complexity features, this was not completely confirmed by our analysis, in which left main or proximal left anterior descending PCI [OR: 0.92 (95% CI: 0.66-1.26); p=0.596] and multivessel PCI [OR: 0.83 (95% CI: 0.56-1.23); p=0.357] were not associated with an increased risk of periprocedural ischemic complications. Conclusions Among NSTEMI patients undergoing PCI, age, coronary bifurcation PCI and stent length ≥ 60 mm represent independent predictive factors of type 4a MI. This finding may have important clinical implications for clinical practice, providing valuable insights for the identification of higher-risk patients that can benefit from a more aggressive treatment.