Introduction: Patients with occlusive arterial disease undergo hypoxia (hyp) in affected limbs & exercise training is used to improve perfusion in the ischaemic tissues. Hyp & exercise increase oxidative stress (Bailey et al., 2009). Oxidative stress has been implicated as a modulator of haemostasis (Görlach, 2005), & as a catalyst for thrombin generation (Wang et al., 2009). We designed a proof-of-concept study in healthy individuals to assess the impact of high-dose antioxidant prophylaxis on the haemostatic system. We hypothesised that since oxidative stress increases global thrombogenicity, the intervention would attenuate changes previously shown by our laboratory (Fall et al., 2011). Methods: Following pre-intervention blood sampling, 40 male subjects were randomly assigned to either a placebo or intervention group. The intervention group were administered 1000mg per day of vitamin C & 900IU per day of vitamin E, & the placebo group were given tablets of identical appearance but no nutritional value for 8 weeks & returned to the laboratory after an overnight fast. Bloods were taken after 10min supine rest in normoxia, after 6 hours of passive exposure to hyp (12% inspired oxygen) in an environmental chamber & after a cycling challenge to volitional exhaustion in hyp. Bloods were batch-analysed for plasma levels of thrombin-antithrombin complex (T-AT), prothrombin fragments 1&2 (PF1+2), activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FB) & d-dimer (DD). Results: Eight weeks intervention significantly increased levels of T-AT and PF1+2 compared to controls (P<0.05) but this difference was abrogated after hyp & remained so after exercise. There were no differences between groups in aPTT, PT, TT, FB or DD in any time point. There were group effects in several markers; aPTT shortened with exercise, as did PT. TT elongated with hyp & remained so post-exercise; there was a reduction in FB with hyp which returned to baseline following exercise. D-dimer remained unchanged. Discussion & conclusions: Increases in T-AT & PF1+2 with intervention suggest an increase in thrombin generation & factor Xa activity (Mannucci, 1994) in the active group. This does not translate into the more routine analysis that would be performed in the patient population. The group data suggest that hyp alone does not affect haemostasis; contrary to existing research (Wang et al., 2009). The addition of exercise hastens both the intrinsic and extrinsic pathways of coagulation in line with previous research (Fall et al., 2011), but this is not translated into down-stream markers, most likely due to activation of antithrombin III. The T-AT & PF1+2 data suggest that free radicals in fact limit thrombin generation at rest. Hyp reverses this, normalising thrombin generation. We are currently focusing on understanding whether the haemostatic:fibrinolytic balance is disturbed.