Background: Cardiac surgery with extracorporeal circulation (ECC) requires the administration of anticoagulant drugs to maintain ACT ranges 400–600 seconds, which requires exhaustive coagulation monitoring for which various point-of-care devices are available. However, there is variability between them, so we aimed to compare the values in ACT measurement. Methods: Simultaneous ACT measurements were performed with the Hemochron Response®, Hemostasis Management System Plus® (HMS Plus®) and Hemochron Signature® systems. Results: A total of 255 simultaneous measurements were taken, the mean and standard deviation (SD) of each device were: Hemochron Signature® 361.1 seconds (SD: 156.9), HMS Plus® 412.8 seconds (SD: 180.9) and Hemochron Response® 422.8 seconds (SD: 187.9), being these differences statistically significant (Fridman’s test p < 0.01). For comparisons the Bland–Altman method was used, resulting the Hemochron Response® has 61.7 seconds higher mean values than the Hemochron Signature®, the Hemochron Response® 10 seconds higher than the HMS Plus® and the HMS Plus® 51.7 seconds higher than the Hemochron Signature®. Conclusion: The differences found in comparisons are considered to be clinically relevant, which is why it is considered important to make the variability of the different monitoring systems known and to take them into account for optimal control of this parameter and its clinical repercussions.