Experimental animal studies on the mechanisms of remote ischaemic conditioning (RIC)-induced cardioprotection against ischaemia/reperfusion injury demonstrate involvement of both neuronal and humoral pathways. Autonomic parasympathetic (vagal) pathways confer organ protection through both direct innervation and/or immunomodulation, but evidence in humans is lacking. During acute inflammation, vagal release of acetylcholine suppresses CD11b expression, a critical beta2-integrin regulating neutrophil adhesion to the endothelium and transmigration to sites of injury. Here, we tested the hypothesis that RIC recruits vagal activity in humans and has an anti-inflammatory effect by reducing neutrophil CD11b expression. Participants (age:50 鈥?/- 鈥?9 years; 53% female) underwent ultrasound-guided injection of local anaesthetic within the brachial plexus before applying 3 鈥媥 鈥? min cycles of brachial artery occlusion using a blood pressure cuff (RIC(block)). RIC was repeated 6 weeks later without brachial plexus block. Masked analysers quantified vagal activity (heart rate, heart rate variability (HRV)) before, and 10 鈥媘in after, the last cycle of RIC. RR-interval increased after RIC (reduced heart rate) by 40 鈥媘s (95% confidence intervals (95%CI):13-66; n 鈥? 鈥?7 subjects; P 鈥? 鈥?.003). RR-interval did not change after brachial plexus blockade (mean difference: 20 鈥媘s (95%CI:-11 to 50); P 鈥? 鈥?.19). The high-frequency component of HRV was reduced after RIC(block), but remained unchanged after RIC (P 鈥? 鈥?.001), indicating that RIC preserved vagal activity. LPS-induced CD16(+)CD11b(+) expression in whole blood (measured by flow cytometry) was reduced by RIC (3615 median fluorescence units (95%CI:475-6754); P = 0.026), compared with 2331 units (95%CI:-3921 to 8582); P = 0.726) after RIC(block). These data suggest that in humans RIC recruits vagal cardiac and anti-inflammatory mechanisms via ischaemia/reperfusion-induced activation of sensory nerve fibres that innervate the organ undergoing RIC.