An increasing number of patients with coronary artery disease are at high operative risk due to advanced age, severe comorbidities, complex coronary anatomy, and reduced ejection fraction. Consequently, these high-risk patients are often offered percutaneous coronary intervention (PCI) as an alternative to coronary artery bypass grafting (CABG). We aimed to investigate the outcome of patients with diabetes mellitus (DM) undergoing high-risk PCI. We analyzed consecutive patients undergoing high-risk PCI (period 01/2016–08/2018). In-hospital major adverse cardiac and cerebrovascular events (MACCEs), defined as in-hospital stroke, myocardial infarction and death, and the one-year incidence of death from any cause were assessed in patients with and without DM. There were 276 patients (age 70 years, 74% male) who underwent high-risk PCI. Eighty-six patients (31%) presented with DM (insulin-dependent DM: n = 24; non-insulin-dependent DM: n = 62). In-hospital MACCEs occurred in 9 patients (3%) with a non-significant higher rate in patients with DM (n = 5/86, 6% vs. n = 4/190 2%; p = 0.24). In patients without DM, the survival rate was insignificantly higher than in patients with DM (93.6% vs. 87.1%; p = 0.07). One-year survival was not significantly different in DM patients with more complex coronary artery disease (SYNTAX I-score ≤ 22: 89.3% vs. > 22: 84.5%; p = 0.51). In selected high-risk patients undergoing high-risk PCI, DM was not associated with an increased incidence of in-hospital MACCEs or a decreased one-year survival rate.