Abstract In the ENSURE-AF study (NCT 02072434), edoxaban was compared to enoxaparin–warfarin in 2199 patients undergoing electrical cardioversion of non-valvular atrial fibrillation (AF). In this multicenter PROBE trial, we analyzed patients randomized to enoxaparin–warfarin. We determined time to achieve therapeutic range (TtTR), time in therapeutic range (TiTR), their clinical determinants, relation to SAMe-TT2 R2 score, and impact on primary endpoints (composite of stroke, systemic embolic event SEE, myocardial infarction MI, and cardiovascular death CVD and composite of major + clinically relevant non-major CRNM bleeding). Among 1104 patients randomized to enoxaparin––warfarin, 27% were oral anticoagulant naïve. Mean age was 64.2±11 years and mean CHA2 DS2 -VASc score was 2.6. Mean TtTR was 7.7 days (median 7 days) and mean TiTR after reaching INR 2.0–3.0 was 71%. In 695 patients with INR <2.0 prior to first dose and who reached ≥2.0, 436 had a SAMe-TT2 R2 score ≤2 and 259 a score of >2. On multivariate regression, an independent predictor of extended TtTR was creatinine clearance (CrCl) P =0.02. TtTR was marginally related to stroke/SEE/MI/CVD ( P =0.06; OR=0.23, 95% CI 0.02–1.17) but not to any bleeding. Independent predictors of TiTR were prior VKA experience ( P <0.01) and low HAS-BLED score ( P =0.02). TiTR was related to any bleeding ( P =0.02; OR=0.39, 95% CI 0.16–0.88), but not stroke/SE/MI/CVD. In this cohort of warfarin users with a high TiTR no difference was seen between TtTR and TiTR in relation to SAMe-TT2 R2 score. In conclusion, even in this short-term study, TiTR was significantly related to bleeding events.