Family history of premature cardiovascular disease (FHpCVD) is a well-established risk factor for development of coronary artery disease. However, little is known about the impact of FHpCVD on the outcome of patients presenting with acute coronary syndrome (ACS). We therefore aimed to evaluate the outcomes of ACS patients grouped by the presence and/or absence of FHpCVD. All patients ≤65 at admission who had an ACS event and were enrolled in the national ACS Israel Survey registry from 2000 to 2013 were included. Patients were grouped by the presence or absence of self-reported FHpCVD. Nearest neighbor propensity score matching was applied to create an evenly matched cohort of patients. Outcomes included 30-day MACE (defined as the composite of death, unstable angina pectoris, myocardial infarction, stroke, stent thrombosis, and urgent revascularization) and its individual components. Of 7,173 ACS patients, 33.9% reported FHpCVD. These patients were younger, with lower prevalence of diabetes, previous cerebrovascular and kidney diseases, but had higher prevalence of smoking and hyperlipidemia (p <0.001 for each). The propensity score-matching cohort included 1,793 pairs of evenly matched patients. The rate of 30-day MACE did not differ in the groups, as well as 1-year mortality (2.4% vs 2.2%, with vs without FHpCVD, respectively). During long-term follow-up (median 7.6 years), mortality rate was lower in the FHpCVD group (hazard ratio 0.82, 95% confidence intervals 0.69 to 0.99). In conclusion, we observed no differences in short- and intermediate-term outcomes based on the presence and/or absence of FHpCVD. However, patients with FHpCVD had better long-term survival.