Background: Direct oral anticoagulants (DOACs) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations., Methods: A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In samples collected as part of routine care DOAC drug concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Anticoagulant intensity at first presentation and drug half-life ( t 1/2 ), tested in repeat samples, were evaluated., Results: A total of 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. Note that 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban-treated patients t ½ was 17.3 hours (95% confidence interval [CI]: 15.4-19.7) without significant difference in both groups (major bleeding: t ½ 16.7 hours, 95% CI: 14.7-19.3; urgent surgery: t ½ 19.7 hours, 95% CI: 15.2-27.9; p = 0.292). In apixaban-treated patients t ½ was 25.0 hours (95% CI: 22.9-27.6) with a longer t ½ after urgent surgery ( t 1/2 : 30.8 hours; 95% CI: 26.9-36.4) compared with severe bleeding ( t 1/2 : 20.8 hours; 95% CI: 18.8-23.2; p < 0.001)., Conclusion: Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer t ½ ., Competing Interests: E.L.-L. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Portola, CSL Behring, and Aspen and institutional research support from Bayer AG, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, and CSL-Behring. I.B. has received speaker's honoraria from Bristol-Myers Squibb/Pfizer, Siemens Healthcare, LFB biomedicaments, and CSL Behring and reimbursement for congress travelling and accommodation from Aspen and Bristol-Myers Squibb. She has performed contract research for Siemens Healthcare and is a member of the advisory board of LFB biomedicaments and of the expert groups of CSL Behring GmbH and Siemens Healthcare Diagnostics Products GmbH. S.K. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, MSD, Actelion, and Daiichi-Sankyo; and institutional research support from Bayer AG, Boehringer Ingelheim, MSD, Actelion, and Daiichi-Sankyo. O.G. has received research funding from Bayer Healthcare, Boehringer Ingelheim, Biotest, CSL Behring, Octapharma, Novo Nordisk, Nycomed, and Portola. He has also received honoraria for lectures and consultancy support from Bayer Healthcare, Boehringer Ingelheim, CSL Behring, Octapharma, Sanofi, Shire, Pfizer, and Portola. U.N.-G. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Octapharma, and LFB. C.v.H. has received honoraria for lectures and consultancy work potentially related to this topic, as well as travel reimbursements from Bayer GmbH, Biotest GmbH, Pfizer GmbH, Daiichi Sankyo, CSL Behring, NovoNordisk GmbH, and HICC GbR. J.B.-W. has received personal honoraria (lectures, advisory boards) and travel support from Bayer, Daiichi Sankyo, Janssen, and Portola and institutional research support from Bayer, Daiichi Sankyo, Janssen, LEO, Pfizer, and Portola. S.S. has received honoraria for lectures from Bayer, Boehringer, Daiichi Sankyo, and Pfizer, grants, and honoraria from BMS. P.M. has received grants from B. Braun Melsungen, CSL Behring, Fresenius Kabi, and Vifor Pharma for the implementation of Frankfurt's Patient Blood Management program and honoraria for scientific lectures from B. Braun Melsungen, Vifor Pharma, Fearing, CSL Behring, and Pharmacosmos. A.G. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer and Daiichi-Sankyo, ASPEN. The other authors report no conflict of interest. The funders had no role in the design of the registry, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)