Objectives: Arterial thrombo-embolic complications (ATEC) are still common during and after non-cardiac arterial procedures (NCAP) despite the administration of (a fixed bolus of) heparin. These ATEC could be due to existing individual differences in heparin sensitivity. The purpose of this study was to evaluate the feasibility and safety of an ACT guided heparin dose protocol and to evaluate if a more effective target ACT can be achieved during NCAP. Methods: In this multi-center prospective study, 194 patients undergoing elective and non-elective NCAP were enrolled and received heparin according to a heparin dose protocol which aimed to obtain a target ACT of 250 seconds (s.), measured by the Medtronic HMS Plus. Patients received a standardized bolus of 5 000 IU followed by additional boluses depending on the actual ACT. Primary outcome was the ACT value reached. Secondary outcomes were incidence of all ATEC and haemorrhagic complications. Results: The mean baseline ACT was 138 ± 17 s. The mean ACT five minutes after the initial heparin bolus of 5 000 IU was 197 ± 31 s. 48% of patients reached an ACT of 200 s. and six per cent of patients reached an ACT of 250 s. Additional dosages of heparin were administered in 72% of patients. With this ACT guided heparin protocol 86% of patients reached an ACT of 200 s. and 26% of patients reached an ACT of 250 s. A negative correlation was found between body weight and the ACT at T1 (P ˂ 0.001). ATEC and haemorrhagic complications occurred in 11.3% and 16.5% of patients. The lowest incidence of ATEC was found in patients with peak ACT between 200 and 250 s, namely 6.3%. Conclusion: This ACT guided heparin protocol proved to be feasible, safe and more patients reached an ACT > of 200 s. compared to a standardized heparin bolus of 5 000 IU. Further research is needed to investigate if ACT guided heparin administration could be preferable over not monitoring the anticoagulant effect of peri-procedural heparin and results in a lower incidence of ATEC, without an increase in haemorrhagic complications.