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Background: Limited data exist on the long-term impact of beta-blocker therapy after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF). Objectives: The aim of the study was to evaluate the effects of early beta-blocker initiation vs no initiation following PCI in patients with stable CAD and preserved LVEF. Methods: This retrospective cohort study employed target trial emulation and incident user design, utilizing the TriNetx database (2009-2024). Early beta-blocker initiation (within days 1 and 7) was compared with no initiation using 1:1 greedy propensity score matching. The outcomes included all-cause mortality, hospitalization for myocardial infarction, heart failure, atrial fibrillation/flutter, stroke, and safety endpoints. Hospitalization for bone fracture and acute appendicitis served as falsification endpoints. In the intention-to-treat analysis, outcomes were analyzed over 5 years using Cox-proportional hazards. Results: Out of 11,681 matched patients per group, beta-blocker therapy was associated with increased all-cause mortality (HR: 1.11 [95% CI: 1.09-1.18]). No significant differences were found in hospitalization for myocardial infarction (HR: 1.03 [95% CI: 0.97-1.09]), stroke (HR: 0.98 [95% CI: 0.91-1.05]), heart failure (HR: 0.99 [95% CI: 0.95-1.03]), and atrial fibrillation/flutter (HR: 0.97 [95% CI: 0.93-1.01]). Hospitalization for hypotension was higher with beta-blockers (HR: 1.10 [95% CI: 1.06-1.14]). Hospitalization for bone fracture (HR: 1.02 [95% CI: 0.85-1.22]) and acute appendicitis (HR: 1.17 [95% CI: 0.95-1.45]) showed no significant associations. Several sensitivity analyses showed consistent results. Conclusions: Early beta-blocker initiation after PCI for stable CAD with preserved LVEF was associated with higher mortality, with no impact on cardiovascular events.