Ischaemia reperfusion injury (IR-injury) occurs when blood supply to a certain area of the body is blocked, and is subsequently followed by reperfusion. During the period of ischaemia, tissue is damaged as a result of lack of oxygen. Rapid reperfusion is mandatory, but unfortunately causes damage in addition to the damage induced by ischaemia alone. While a prolonged period of ischaemia is harmful to the bodily tissue, short periods of ischaemia interspersed with short bouts of reperfusion have protective effects. This mechanism is called ischaemic preconditioning (IPC). In this thesis, the impact of co-morbidity and age on IR-injury and IPC are explored. Moreover, the possible role of IPC to enhance exercise performance is investigated. Finally an attempt is made to understand the interchangeable effects of IPC and exercise performance in the prevention of IR-injury. Using the brachial artery endothelial function as a surrogate marker, first the consequences of IR-injury in both young and older individuals on endothelial function were studied. It was also assessed whether IPC could prevent endothelial IR-injury. It was found that endothelial function in both groups declined, when IR-injury was not preceded with IPC. However, when IPC was applied prior to IR-injury, a protective effect was detected in young subjects, but not in older participants. In chapter 5, this study was repeated in patients with heart failure, as they are at an increased risk for IR-injury. While in both groups a significant decline in endothelial function was observed, a much larger decline was established in the heart failure group. Moreover, IPC failed to protect against endothelial dysfunction in heart failure patients after IR-injury. The third study presented in this thesis, focused on the question whether exercise performance enhancement during a 5-km time trial was comparable when IPC on the upper legs was applied immediately before the time trial versus 24 hours (24-IPC) prior to exercise. Interestingly, a significant and strong correlation was found in finish time between acute IPC and 24-IPC, suggesting comparable effects of IPC and 24-IPC on exercise performance. In a follow-up study, it was determined whether local IPC applied on the upper arm, or remote IPC applied on the legs, would lead to an improved maximum incremental arm crank exercise test in individuals with a complete spinal cord lesion. The main finding was that upper arm IPC led to an increased performance enhancement, whilst remote IPC (stimulus below the lesion) did not lead to any significant differences. These studies help to inform the best or most practical application of IPC in daily life situations. Some previous work has suggested that exercise may resemble some of the effects of IPC. More specifically, acute exercise might possess the same protective effects against ischaemia-reperfusion injury as IPC. Therefore, in young healthy individuals it was studied, whether an acute bout of endurance or interval exercise is able to protect against brachial endothelial IR-injury. It was established that interval exercise prevented endothelial dysfunction after an IR stimulus, while no protective effect of endurance exercise was found. It was concluded that interval exercise, but not endurance exercise, prevented endothelial dysfunction after an ischaemic period. In conclusion, this thesis provides further evidence for the protective effects of (remote) IPC, both on the prevention of endothelial IR-injury as well as improvement in exercise performance. However, effects may depend on the protocol and population studied.