The cardioprotective benefits of exercise are partly explained via long term improvements in cardiovascular risk factors and/or physiological remodelling of (coronary) arteries. In animal models a single bout of running can offer immediate cardioprotection (Hoshida et al., 2002). Ischaemic preconditioning (IPC) using a blood pressure cuff to cause a cyclical bout of non-lethal ischemia also offers cardioprotection against ischaemic injury which is evident when IPC is performed locally (at site of injury) or remotely (site distant to injury e.g. forearm) (Kharbanda et al., 2002). Our aim was to compare handgrip exercise and forearm IPC on the ability to attenuate local and remote endothelial ischaemia reperfusion (IR)-injury, a surrogate for coronary artery IR-injury in humans. Following ethical approval, six healthy males (age 24±4 years; BMI 24.6±1.73) attended the laboratory on 3 occasions. During each visit bilateral brachial artery flow-mediated dilation [(FMD) Thijssen et al., 2019) was examined at rest, immediately following an intervention and following 15-minute upper-arm occlusion (220 mm Hg) with 15-minute reperfusion to induce a temporary endothelial IR-injury. Prior to the IR-injury, participants performed either 4×5 minutes 50% maximal voluntary contraction unilateral handgrip exercise (which mimicked the blood flow pattern evident during 4×5 minutes of IPC in pilot data collection), were administered unilateral IPC (220 mm Hg, 4×5 minutes) or rested in the supine position (control) in a randomised and counterbalanced order. Data were analysed using repeated measures general linear models and reported as change from rest with 95% confidence intervals. The change in FMD from rest to immediately following the intervention in the local arm was similar with handgrip exercise, IPC and control, 3.05% (1.05, 5.05), 1.80% (0.78, 2.81) and 0.75 % (-1.47, 2.97) respectively (P = 0.19). A similar change was evident in the remote arm (P = 0.60). Both handgrip exercise (1.02% [-0.26, 2.29]) and IPC (0.43% [-3.36, 4.22]) displayed an attenuation in the decline in FMD following an IR-injury compared to control (-0.89% [-3.26, 1.48] in the local arm. In the remote arm, handgrip exercise, IPC and control were -2.2% (-5.4, 1.0), -1.4 (-3.87, 1.07) and -2.3 (-5.8, 1.01%), respectively following an IR-injury. Both handgrip exercise and IPC can attenuate brachial artery endothelial IR injury. If these benefits of handgrip exercise translate to remote areas, like with IPC, this may have clinical benefit when implementing prior to planned ischemia reperfusion injuries (e.g. cardiac surgery) or in individuals who are at increased risk of an myocardial infarction.