Background <p>Patients with atrial fibrillation (AF) often underwent percutaneous coronary intervention (PCI), and the complexity of PCI has risen in recent years. However, there is limited data available on clinical outcomes in patients with AF who underwent complex PCI.</p> Methods <p>This was a prospective, observational study. Complex PCI was defined as PCI performed to ≥ 3 separate major coronary vessels; ≥3 stents implanted; ≥3 lesions treated; or total stented length &gt; 60&#xa0;mm. The primary outcome was defined as major adverse cardiovascular event (MACE) including all-cause death, spontaneous myocardial infarction (MI), stroke/ transient ischemic attack (TIA), systemic embolism or ischemia-driven revascularization. The secondary outcome was defined as net adverse clinical events (NACE), which included major adverse cardiovascular events (MACE) and major bleeding.</p> Results <p>A total of 1132 patients who underwent PCI with AF were enrolled consecutively. The mean age was 67 ± 9, and 75.1% were male. 320 participants (28.2%) underwent complex PCI. During a median follow-up of 1045 days (interquartile range: 666–1327), the primary outcome occurred in 52 out of 320 patients (16.2%), while the secondary outcome was observed in 55 out of 320 patients (17.2%) in the complex PCI group. MACE showed no differences between groups (hazard ratio [HR], 1.30; 95% confidence interval [CI], 0.93–1.82), nor did NACE (HR:1.34, 95%CI: 0.97–1.85). Patients with complex PCI still had a higher likelihood of experiencing spontaneous MI (HR, 2.17, 95%CI, 1.00-4.70) and ischemic driven revascularization (HR, 1.86, 95%CI, 1.01–3.45) after adjusted for confounders.</p> Conclusion <p>The complexity of PCI was an independent risk factor for adverse clinical outcomes, particularly for myocardial infarction and revascularization events in patients with atrial fibrillation. However, it was not associated with major bleeding, all-cause mortality, or stroke/TIA.</p> Clinical trial number <p>Not applicable</p>