AimsWe investigated the differences in prevalence of acute coronary syndrome (ACS) by presence versus absence of diabetes in males and females with chest discomfort who called out-of-hours primary care (OHS-PC). MethodsA cross-sectional study performed in the Netherlands. Patients who called the OHS-PC in the Utrecht region, the Netherlands between 2014 and 2017 with acute chest discomfort were included.We compared those with diabetes with those without diabetes. Multivariable logistic regression was used to determine the relation between diabetes and (i) high urgency allocation and (ii) ACS. ResultsOf the 2,195 callers with acute chest discomfort, 180 (8.2%) reported having diabetes. ACS was present in 15.3% of males (22.0% in those with diabetes) and 8.4% of females (18.8% in those with diabetes). Callers with diabetes did not receive a high urgency more frequently (74.4% vs. 67.8% (OR: 1.38; 95% CI 0.98–1.96). However, such callers had a higher odds for ACS (OR: 2.17; 95% CI 1.47–3.19). These differences were similar for females and males. ConclusionsDiabetes holds promise as diagnostic factor in callers to OHS-PC with chest discomfort. It might help triage in this setting given the increased risk of ACS in those with diabetes.