Aims: We aimed to investigate the impact of percutaneous coronary intervention (PCI) and diabetes mellitus (DM) on short- and long-term prognosis in patients with coronary artery disease using three-vessel quantitative flow ratio (3 V-QFR) assessment.Methods: A retrospective analysis of 2440 vessels in 1181 patients who underwent PCI was performed. The patients were categorized according to the presence or absence of DM and the median 3 V-QFR. The primary outcome was the occurrence of major adverse cardiac events (MACE), defined as a combination of cardiovascular death, myocardial infarction, and ischemia-driven revascularization, over a 5-year period.Results: The pre-PCI and post-PCI 3 V-QFR values for the entire population were 2.37 (2.04-2.56) and 2.94 (2.82-3.00), respectively. Landmark analysis showed that the incidence of MACE was comparable among all groups within the first year (log-rank p = 0.088). Over the course of 2 years, the incidence of MACE was higher in both groups with a post-PCI 3 V-QFR < 2.94 (log-rank p < 0.001). However, from 2 to 5 years, patients with DM had higher rates of MACE (log-rank p = 0.013).Conclusions: In the short term, a low post-PCI 3 V-QFR is a predictor of high risk for MACE. However, in the long term, DM emerges as the dominant risk factor.