Suboptimal medication adherence to anticoagulation therapy is a widespread problem and is associated with increases in risk of thromboembolic or haemorrhagic events. Standard therapy with warfarin is associated with suboptimal adherence due to narrow therapeutic window, frequent side effects and need for INR control. Much shorter half-life of NOACs raises the question of optimal dosing regimen. Higher efficacy and safety of twice-daily dosing regimen of NOACs is based on the results of pharmacokinetic models, data from phase 2 and phase 3 trials and metanalysis of 4 phase 3 trials. Twice-daily dosing regimen of apixaban reflects the priority of clinical outcomes. AVERROES, ARISTOTLE and AMPLIFY trials provide strong evidence of efficacy and safety of twice-daily dosing regimen of apixaban. First results of AEGEAN-trial have shown high adherence and persistence to apixaban.