There is a lack of long-term outcome data supporting the role of nurses in cardiovascular (CV) risk management. The ALLEPRE [ALLiance for sEcondary PREvention after an acute coronary syndrome (ACS)] trial was a pragmatic, randomized, multicentre, interventional trial comparing the efficacy of a nurse-coordinated prevention program (NCPP) with standard of care (SOC). The NCPP patients attended nine individual educational sessions over four years at which a centrally trained nurse provided counselling aimed at identifying CV risk factors and encouraging healthier lifestyles and medication adherence; the SOC patients followed the standard practices of their hospitals. The trial's primary endpoint was the composite of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke (MACE). A total of 2057 ACS patients were randomized 1:1 to the NCCP (n=1031) or SOC group (n=1026). In comparison with SOC, the NCPP significantly reduced MACE [16.2% vs 22.6%; hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.57-0.85; P-value <0.001], a benefit mainly driven by a reduction in non-fatal MI (9.3% vs 15.2%; HR 0.60; 95% CI 0.46-0.77; P-value=0.0001). The occurrence of the pre-specified secondary outcome of MACE plus ischaemia-driven revascularization was significantly reduced (HR 0.77, 95% CI 0.64-0.92; P-value= 0.005). Exercise frequency (P<0.0001), body weight control (P=0.003), and medication adherence (P<0.001) improved more in the NCPP group. The NCPP significantly reduced long-term MACE, improved physical activity, body weight control, and pharmacotherapy adherence in post-hospitalization ACS patients. Including an NCPP in healthcare provision may contribute to the successful implementation of secondary prevention strategies.