Anticoagulation therapy is essential for patients with mechanical heart valve prostheses to prevent thromboembolic events. Warfarin and acenocoumarol are the most commonly used vitamin K antagonists (VKAs). This report presents the case of a 70-year-old woman with a mechanical mitral valve who had persistent difficulty maintaining an adequate International Normalized Ratio (INR) while on acenocoumarol.The patient, who underwent mechanical mitral valve replacement seven years earlier, was managed with acenocoumarol and attended regular follow-ups with consistent INR monitoring. Despite this, her INR remained outside the therapeutic range (2.5–3.5) for almost one year, with fluctuations both above and below the target. This unstable control increased the risk of thromboembolic and bleeding complications. Given the repeated difficulties in achieving stable anticoagulation, clinicians decided to switch her to warfarin, a VKA with a longer half-life and more predictable pharmacokinetics. Transition to warfarin was performed with careful dose titration and bridging with low-molecular-weight heparin until reaching INR > 2. Subsequent monitoring aimed to stabilize anticoagulation. After two months on warfarin, the patient’s INR consistently remained within the therapeutic range, reflecting markedly improved control compared with her previous treatment with acenocoumarol.This case illustrates the challenges of anticoagulation management in patients with mechanical valves and highlights the need to individualize therapy based on clinical response.Although both VKAs are effective, elderly patients often exhibit greater INR variability with acenocoumarol. The patient’s improvement after transitioning to warfarin supports its potential advantage in achieving more stable anticoagulation.Current evidence, including the PLECTRUM study, shows that time in therapeutic range is significantly higher with warfarin than with acenocoumarol in patients with mechanical prostheses, regardless of comorbidities or clinical characteristics. These findings suggest superior INR stability with warfarin. Earlier studies, such as Barcellona et al., reported no major differences in INR control but noted fewer overdosing episodes with warfarin. Overall, accumulated data favor warfarin due to its longer half-life and more consistent anticoagulant effect.In conclusion, warfarin is generally preferred over acenocoumarol in patients with mechanical prostheses owing to its superior INR stability, although acenocoumarol may remain an option in selected circumstances.