Significant variability in activated clotting time (ACT) measurement exists based on the type of point-of-care system used. We sought to determine the degree of agreement in ACT measurements by the Hemochron Response and the Hemochron Signature Elite Whole Blood coagulation systems and whether these 2 systems can be used interchangeably. We prospectively compared 126-paired samples in 77 patients undergoing percutaneous coronary intervention. ACT was measured for each sample using the Hemochron Response system with glass test tubes and the Hemochron Signature Elite system with low-range ACT cuvettes simultaneously. We used correlation and Bland-Altman analyses. Mean age of the study cohort was 67 ± 11 years, 49% were women, and 65% of measurements were made after systemic anticoagulation. There was a significant correlation between the Hemochron Response and Hemochron Signature Elite systems (r = 0.84, p <0.01). However, the mean bias for the ACT measurement was 9 seconds (95% confidence interval -69 to 86). In the therapeutic range of ACT measurements, the mean bias was 15 seconds (95% confidence interval -60 to 91). Thirty-three percent of total samples had >10% disagreement and 8% of samples had >20% disagreement in the ACTs measured with the Hemochron Response compared to the Hemochron Signature Elite. In conclusion, the Hemochron Response and Hemochron Signature Elite ACT values cannot be used interchangeably. Institutions using these 2 devices should be cognizant of this difference for ensuring patient safety.