Many studies have reported comparable risk of hard end points between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for unprotected left main coronary artery (ULMCA) stenosis. However, there are limited data regarding the morbidity associated with ULMCA revascularization. This study sought to compare the cause and risk of readmissions after PCI and CABG for ULMCA stenosis. We evaluated the unadjusted and adjusted risk of readmissions in 1,352 patients (783 PCI treated and 569 CABG treated) who were consecutively enrolled in a multicenter registry of patients with ULMCA stenosis, named the Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease trial. Overall, 206 PCI-treated patients (26.3%) experienced at least 1 readmission after the index procedure during 48.7 ± 16.0 months of follow-up compared with 84 CABG-treated patients (14.8%, p <0.001). The most frequent causes of readmission were repeat revascularization after PCI (41%) and noncardiac readmissions after CABG (48%). Through repeated events analysis, PCI was associated with more frequent readmissions than CABG (hazard ratio 2.037, 95% confidence interval 1.542 to 2.692, p <0.001), being an independent predictor of readmission (hazard ratio 1.820, 95% confidence interval 1.420 to 2.331, p <0.001). Except for the acute period, defined as the first 3 months, when there was no significant difference in readmission rate, a higher readmission rate after PCI was consistently observed over the remainder of the follow-up period. In conclusion, PCI was shown to be associated with a higher risk of readmission than CABG in treating ULMCA disease. This higher risk was attributable to more frequent revascularization in the PCI group.