Vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) are beneficial in patients with stroke and atrial fibrillation (AF). However, little is known about frequency and determinants of adherence to NOACs/VKAs in clinical practice. This is a single-center explorative study from the Novel Oral Anticoagulants in Stroke Patients (NOACISP)-LONGTERM registry. We included consecutive AF-stroke patients treated with NOACs/VKAs and followed up for 3-24 months. Adherence was assessed at follow-up using structured interviews and quantified as the proportion of prescribed doses taken (PDT). Outcome measures were (i) full adherence, (ii) ≥95% adherence and (iii) ≥80% adherence (i.e., PDT 100/≥95/≥80%). To explore determinants of full adherence, we compared characteristics of fully and non-fully adherent patients. A total of 218 of 251 (86.9%) patients (48% female, mean age 77.9 ± 9.1 years, 78% NOACs; 22% VKAs) were eligible for analysis with a median follow-up of 12 months: fully adherent were 78.4% patients (NOACs 77.1%, VKAs 83.3%, p = 0.35), ≥95% adherent were 95.4% and ≥80% adherent were 97.2%. Fully adherent patients took more pills daily (median (interquartile range) 7 (5-10) vs. 6 (4-8), p = 0.039), had more often previous antithrombotic treatment (70.8 vs. 53.2%, p = 0.023), caregiver-assisted medication administration (54.2 vs. 19.1%, p < 0.001) and functional dependency (32.8 vs. 15%, p = 0.011) than non-fully adherent patients. Full adherence was frequent. Patients naïve to antithrombotics, taking few pills, which they self-administer, were at the highest risk of non-adherence and may benefit most from adherence-enhancing interventions.