The REDUCE-IT trial investigated the effects of icosapent ethyl (IPE) in patients with acute coronary syndrome (ACS). The trial randomized 8179 statin-treated patients with controlled LDL cholesterol and elevated triglycerides to either 4 g IPE or placebo. The primary outcome was a composite of cardiovascular death, non-fatal MI, non-fatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary outcome was a composite of cardiovascular death, non-fatal MI, or non-fatal stroke. Among the 8179 patients, 840 had recent ACS (<12 months before randomization). IPE reduced the incidence of the first primary composite outcome by 37% (HR 0.63; 95% CI 0.48–0.84, P = .002) and total primary composite outcomes by 36% (RR 0.64; 95% CI 0.45–0.90, P = .01). Absolute risk reduction in the first primary outcome with IPE was 9.3% (NNT 11). In contrast, the benefits were less in patients with ACS ≥12 months before randomization, with a relative risk reduction of 22.0% and an absolute risk reduction of 4.7% (NNT 21). In recent ACS patients, IPE reduced the incidence of the first key secondary composite outcome by 36% (HR 0.64; 95% CI 0.44–0.92, P = .01) and total key secondary composite outcomes by 28% (RR 0.72; 95% CI 0.47–1.09, P = .12). IPE also reduced the composite of cardiovascular death and non-fatal MI by 36% (HR 0.64; 95% CI 0.43–0.96, P = .03) and urgent or emergent revascularization by 44% (HR 0.56; 95% CI 0.36–0.87, P = .009). In recent ACS patients, the proportion of patients with at least one treatment-emergent adverse event did not differ between treatment arms. However, the risk of atrial fibrillation or flutter was increased with IPE. The results suggest that IPE significantly reduces ischaemic cardiovascular events in high-risk patients with recent ACS without increased bleeding. This supports the initiation of IPE in REDUCE-IT-eligible patients as soon as possible after ACS.The REDUCE-IT trial investigated the effects of icosapent ethyl (IPE) in patients with acute coronary syndrome (ACS). The trial randomized 8179 statin-treated patients with controlled LDL cholesterol and elevated triglycerides to either 4 g IPE or placebo. The primary outcome was a composite of cardiovascular death, non-fatal MI, non-fatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary outcome was a composite of cardiovascular death, non-fatal MI, or non-fatal stroke. Among the 8179 patients, 840 had recent ACS (<12 months before randomization). IPE reduced the incidence of the first primary composite outcome by 37% (HR 0.63; 95% CI 0.48–0.84, P = .002) and total primary composite outcomes by 36% (RR 0.64; 95% CI 0.45–0.90, P = .01). Absolute risk reduction in the first primary outcome with IPE was 9.3% (NNT 11). In contrast, the benefits were less in patients with ACS ≥12 months before randomization, with a relative risk reduction of 22.0% and an absolute risk reduction of 4.7% (NNT 21). In recent ACS patients, IPE reduced the incidence of the first key secondary composite outcome by 36% (HR 0.64; 95% CI 0.44–0.92, P = .01) and total key secondary composite outcomes by 28% (RR 0.72; 95% CI 0.47–1.09, P = .12). IPE also reduced the composite of cardiovascular death and non-fatal MI by 36% (HR 0.64; 95% CI 0.43–0.96, P = .03) and urgent or emergent revascularization by 44% (HR 0.56; 95% CI 0.36–0.87, P = .009). In recent ACS patients, the proportion of patients with at least one treatment-emergent adverse event did not differ between treatment arms. However, the risk of atrial fibrillation or flutter was increased with IPE. The results suggest that IPE significantly reduces ischaemic cardiovascular events in high-risk patients with recent ACS without increased bleeding. This supports the initiation of IPE in REDUCE-IT-eligible patients as soon as possible after ACS.