Objectives Diabetes mellitus (DM) and metabolic syndrome (MS) are both associated with heart attack. Evidence regarding which condition-MS or DM-is better associated with heart attack, however, is limited. The purpose of this study is to examine DM and MS, and their comparative associations with heart attack, using the 2015 Behavioral Risk Factor Surveillance System (BRFSS). Design Cross-sectional study. Methods A total of 332008 subjects aged over 18 years were included in the analysis. All subjects were classified into four groups based on their DM and MS status: neither DM nor MS, DM without MS, MS without DM, and both DM and MS. A weighted hierarchical logistic regression was used to examine the difference between the four groups in their association with the risk of a heart attack. Results Differences in weighted frequency distributions of gender, age category (over 45 years or not), smoking status, education, race, physical activity and daily vegetable and fruit consumption were significantly different across the four groups (p<0.05). The weighted prevalence of heart attack was 5.2% for neither DM nor MS group, 8.5% for DM without MS group, 11.0% for MS without DM group and 16.1% for both DM and MS group. The weighted prevalence of heart attack in MS without DM group was significantly higher than that in the DM without MS group (p<0.01). After adjusting for confounding variables, DM without MS and MS without DM were both found to be independently associated with heart attack compared with those without DM nor MS (DM without MS, OR=2.09; MS without DM, OR=2.58, all p<0.01). Conclusion The BRFSS 2015 data indicated that MS without DM and DM without MS had comparable effects on heart attack, and the odds of risk are doubled than US adults with neither DM nor MS.