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Percutaneous coronary intervention (PCI) is increasingly performed for symptom relief and survival benefit, particularly in patients presenting with acute coronary syndromes. It remains controversial whether prior PCI, and specifically when index PCI is performed on previously treated lesion(s), affects peri-procedural and in-hospital mortality. We queried an institutional PCI registry for all unique patients undergoing PCI during a 4-year period and classified them as having had or not prior PCI. If prior PCI had occurred, we further defined index PCI as a target lesion (TLR) PCI or non-TLR PCI, according to lesion(s) treated during the prior PCI. Multivariable analysis was performed to identify predictors of in-hospital mortality. Prior PCI was an independent predictor of in-hospital survival or lower mortality (HR 0.41 [0.22-0.76], P = 0.004), together with lower age (per 5 years, HR 0.73 [0.66-0.82], P < 0.001) and elective PCI (HR 0.63 [0.58-0.70], P < 0.0001). Among prior PCI patients, TLR PCI was associated with higher mortality (HR 3.03 [1.05-8.33]. P = 0.045), while elective PCI status was associated with lower mortality (HR 0.10 [0.01-0.80], P = 0.03). This excess mortality was only present in non-elective PCI cases (P INT = 0.02). We conclude that PCI mortality risk is decreased in patients with prior PCI, particularly when index PCI is performed electively on a lesion not previously treated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)