Background Data are still limited regarding whether there are differential long‐term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting ( CABG ) for left main coronary artery disease with or without diabetes mellitus ( DM ). Methods and Results Using the 10‐year data from the MAIN ‐ COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry, we sought to examine the effect of DM on comparative outcomes after percutaneous coronary intervention or CABG in patients with unprotected left main coronary artery disease. The outcomes of interest were all‐cause mortality; a composite of death, Q‐wave myocardial infarction, or stroke; and target‐vessel revascularization. The primary adjusted analyses were performed with the use of propensity scores and inverse‐probability weighting. Of 2240 patients with left main coronary artery revascularization, 722 (32%) had DM . In the overall population, the adjusted 10‐year risks of death and composite outcome were similar between percutaneous coronary intervention and CABG , irrespective of DM status ( P interaction : 0.41, mortality; 0.40, composite outcome). However, in the cohort of bare‐metal stents and concurrent CABG , we observed differential outcomes after stenting and CABG by DM status ( P interaction : 0.09, mortality; 0.04, composite outcome), favoring CABG in patients with DM. In the cohort of drug‐eluting stents and concurrent CABG , the better effect of CABG over stenting was narrowed in patients with DM without a significant interaction ( P interaction : 0.63, mortality; 0.47, composite outcome). Conclusions In this cohort of patients with longest follow‐up who underwent left main coronary artery revascularization, the clinical impact of DM favoring CABG over percutaneous coronary intervention has diminished over time from the bare‐metal stent to the drug‐eluting stent era. Registration URL : http://www.clini​caltr​ials.gov . Unique identifier: NCT 02791412.