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Description: Despite the number of studies reporting effective treatments in animal models of ischemic stroke, translation into clinical success in humans has failed. Multiple factors might influence this translational gap. Among these are discrepancies in the populations studied. While most human stroke patients are elderly, both male and female, and with often one or more comorbidities, preclinical research in animals is usually performed using young, healthy, male rodents. The most common comorbidities in human stroke patients include hypertension, diabetes and obesity. Preclinical research considering age or comorbidities often show alterations in infarct volume and treatment effect. In this review we will focus on the effect of arterial hypertension on stroke outcomes and aim to investigate the body of preclinical ischemic stroke evidence on: the effect of comorbidities on stroke outcomes treatment efficacy in animals with comorbidities. We will focus our investigation on stroke with middle cerebral artery occlusion since this is most common in the human pathological condition and furthermore the most abundant animal model in stroke research.8 This is the third of a series of three systematic reviews aiming at identifying the influence of 1) ageing (http://syrf.org.uk/protocols/), 2) diabetes mellitus, obesity, and metabolic syndrome (DOI: 10.17605/OSF.IO/9BWGS) and 3) arterial hypertension on stroke outcome and treatment efficacy in preclinical stroke models.