This study aimed to investigate the dynamic skin perfusion via hyperspectral imaging (HSI) after application of Articaine-4% ± epinephrine as well as epinephrine only. After the subcutaneous injection of (A100) Articaine-4% with epinephrine 1:100,000, (A200) Articaine-4% with epinephrine 1:200,000, (Aw/o) Articaine-4% without epinephrine, and (EPI200) epinephrine 1:200,000, into the flexor side of the forearm in a split-arm design, dynamic skin perfusion measurement was performed over 120 min by determining tissue oxygen saturation (StO2) using HSI. After injection, all groups experienced a reactive hyperaemia. With A200, it took about three min for StO2 to drop below baseline. For Aw/o and EPI200, perfusion reduction when compared to baseline was seen at 30 min with vasoconstriction >120 min. A100 caused vasodilation with hyperaemia >60 min. After three minutes, the perfusion pattern differed significantly (p < 0.001) between all groups except Aw/o and EPI200. The vasoactive effect of epinephrine-containing local anaesthetics can be visualised and dynamically quantified via StO2 using HSI. Aw/o + epinephrine 1:100,000 and 1:200,000 leads to perfusion reduction and tissue ischaemia after 30 min, which lasts over 120 min with no significant difference between both formulations. When using Aw/o containing epinephrine in terms of haemostasis for surgical procedures, a prolonged waiting time before incision of 30 or more min can be recommended.