Abstract Background The performance of the GRACE, HEART and TIMI scores were compared in predicting the probability of major adverse cardiac events (MACE) in chest pain patients presenting at the emergency department (ED), in particular their ability to identify patients at low risk. Methods Chest pain patients presenting at the ED in nine Dutch hospitals were included. The primary outcome was MACE within 6 weeks. The HEART score was determined by the treating physician at the ED. The GRACE and TIMI score were calculated based on prospectively collected data. Performance of the scores was compared by calculating AUC curves. Additionally, the number of low-risk patients identified by each score were compared at a fixed level of safety of at least 95% or 98% sensitivity. Results In total, 1748 patients were included. The AUC of GRACE, HEART, and TIMI were 0.73 (95% CI: 0.70–0.76%), 0.86 (95% CI: 0.84–0.88%) and 0.80 (95% CI: 0.78–0.83%), respectively (all differences in AUC highly statistically significant). At an absolute level of safety of at least 98% sensitivity, the GRACE score identified 231 patients as “low risk” in which 2.2% a MACE was missed; the HEART score identified 381 patients as “low risk” with 0.8% missed MACE. The TIMI score identified no “low risk” patients at this safety level. Conclusions The HEART score outperformed the GRACE and TIMI scores in discriminating between those with and without MACE in chest pain patients, and identified the largest group of low-risk patients at the same level of safety.