Introduction: Obstructive sleep apnoea (OSA) is associated with increased cardiovascular risk, however the mechanisms are not well established. Objectives: This study aimed to determine whether treatment of OSA with nasal continuous positive airway pressure (CPAP) would favourably alter coagulability across the sleep-wake cycle. Methods: In a randomised crossover trial, 28 patients received therapeutic or placebo CPAP, each for 2 months with a 1 month washout between treatments. After each treatment period, a 24 h coagulation study was conducted in the laboratory. Plasminogen activator inhibitor-1 (PAI-1), D-dimer, fibrinogen, von Willebrand Factor (vWF), factor VIII (FVIII), factor VII (FVII) and factor V (FV) were determined at seven time points over the day and night. Results: At baseline, patients had severe OSA (Apnoea Hypopnoea Index 37.9623.9 events/h). Treatment of OSA with CPAP compared with placebo resulted in lower 24 h levels of vWF (-3.9%, p=0.013), FVIII (-6.2%, p=0.007) and FV (-4.2%, p<0.001). The greatest difference occurred during the nocturnal and early morning periods. In contrast, fibrinogen, D-dimer, FVII and PAI-1 did not differ between treatments, however all markers displayed diurnal variability independent of treatment. Conclusions: In this randomised, placebo-controlled crossover trial, treatment of OSA with CPAP reduced the early morning level of vWF, and nocturnal levels of FVIII and FV. These findings suggest that CPAP may reduce cardiovascular risk in OSA, in part through reducing risk of thrombosis.