We aimed to provide detailed utilization data on the total use of non-vitamin K antagonist oral anticoagulants (NOACs) since their introduction in 2008. Using the nationwide Danish National Prescription Registry, we identified all individuals filling prescriptions for NOACs 2008-2016. We reported the development in incident and prevalent users and explored baseline characteristics and treatment persistence according to treatment indication. A total of 126,691 NOAC users were identified within the Danish population of 5.7 million inhabitants. The annual incidence and prevalence increased rapidly reaching 10 and 17 per 1000 individuals in 2016. Patients received NOACs due to atrial fibrillation (AF) (43%), venous thromboembolism (VTE) prophylaxis after arthroplastic surgery (17%), VTE (12%) and no registered indication (28%). The most frequently used NOAC was rivaroxaban (n = 52,431), followed by dabigatran (n = 47,067), apixaban (n = 27,116) and edoxaban (n = 77). The proportion of AF and VTE patients initiating low-dose NOACs were between 23% and 50%. Patients treated with NOAC for VTE primarily received rivaroxaban. We observed a trend towards increased use of apixaban and rivaroxaban at the expense of dabigatran. Treatment persistence was highly dependent on treatment indication. Persistence to NOAC after 3 years was only 62% in AF compared to 28% for VTE. We documented an accelerating increase in the use of all four NOACs in the first 8 years after introduction. We have identified areas requiring further attention, including reasons for missing indications, potential inappropriate dosing and low long-term persistence with NOACs in patients with AF.