Background Statins may exert a protective effect against the risk of venous thrombosis (VT), but the mechanism is unclear. Objectives In this open-label, randomized clinical trial ( NCT01613794), we aimed to determine the ex vivo effect of rosuvastatin on platelet reactivity in patients with a history of VT. Methods Platelet reactivity, in platelet reaction units (PRUs), was measured at baseline and after 28 days with VerifyNow, which uses arachidonic acid to determine thromboxane-mediated platelet aggregation, in 50 consecutive patients included in our study (25 receiving rosuvastatin and 25 without intervention). Results Forty-seven of 50 (94.0%) consecutively enrolled patients had two valid PRU measurements. The mean PRUs in rosuvastatin users were 609 at baseline and 613 at the end of the study (mean change 5; 95% confidence interval [CI] - 18 to 27). The mean PRUs in non-users were 620 at baseline and 618 at the end of the study (mean change - 2; 95% CI - 15 to 12). The mean difference in PRU change between users and non-users was 6 (95% CI - 20 to 33). After exclusion of patients who used antiplatelet medication, or had thrombocytopenia, similar results were obtained, i.e. no apparent effect of rosuvastatin on PRUs, with a mean difference in PRU change between users and non-users of - 1 (95% CI - 20 to 19). Conclusions Rosuvastatin does not affect platelet reactivity when arachidonic acid is used as an agonist in patients with a history of VT.