Background <p>Non-hyperemic pressure ratios are recommended to assess intermediate coronary lesions. Evidence on outcomes after deferral of revascularization based on resting full-cycle ratio (RFR) remains limited.</p> Objective <p>This study aimed to assess clinical outcomes over 2&#xa0;years following revascularization deferral guided by RFR.</p> Methods <p>We analyzed 773 patients with 1012 intermediate coronary lesions undergoing RFR assessment between 2016 and 2022 at the University Hospital Cologne resulting in revascularization deferral. Lesions were stratified into three RFR groups: &lt; 0.93, 0.93–0.95, and &gt; 0.95. The primary endpoint was the 2-year incidence of major cardiac adverse events (MACE), defined as a composite of cardiovascular death, myocardial infarction, or stroke.</p> Results <p>Patients presented with silent ischemia (35.4%), stable (30.9%) or atypical angina (20.1%), and unstable angina (13.6%). Over 2-year MACE occurred in 8.1% of lesions and 7.8% of patients, while death of any cause was documented in 86 patients (11.1%). MACE were similar across RFR groups, though target-vessel revascularization and target-vessel ischemia-driven revascularization were more frequent in patients with RFR &lt; 0.93 (HR, 3.14 [95% CI 1.35–7.30, <i>p</i> = 0.008 and 2.42 [95% CI 1.01–5.84], <i>p</i> = 0.048). Chronic obstructive pulmonary disease, age, peripheral artery disease, atrial fibrillation, diffuse coronary disease, and heavy calcification were associated with 2-year MACE.</p> Conclusions <p>In this all-comers cohort, the 2-year MACE-rate after RFR-guided deferral was 8.1%. Higher revascularization rates in lesions with RFR ≤ 0.93 suggest the need for further evaluation, especially in the presence of high-risk features.</p> Graphical Abstract <p>Central Illustration: Long-Term outcomes after RFR and deferral of revascularization</p> <p></p>