The abnormalities in blood coagulation in patients with diabetes can lead to a prothrombotic state and requirement for the administration of direct anticoagulants. However, no comparative studies have been conducted on the effects of different direct anticoagulants. A head-to-head investigation of the impact of anticoagulants in 50 patients of type 1 diabetes mellitus (DMT1) was performed, and the data were compared to 50 generally healthy individuals. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured in plasma treated with vehicle, heparin, or four direct anticoagulants at 1 μM. In addition to common biochemical parameters, novel inflammatory markers (neopterin, kynurenine/tryptophan ratio) and major vitamin K forms were measured. Heparin and dabigatran treatments resulted in prolonged coagulation in DMT1 patients compared to healthy individuals in both tests (both p < 0.001). The same phenomenon was observed for rivaroxaban and apixaban-treated samples in PT (p < 0.001). Interestingly, healthy volunteers had higher total vitamin K levels than DMT1. Further analysis suggested that observed coagulation differences were not caused by differences in glycemia but were rather associated with an unexpected, better lipid profile of our DMT1 group. There were also correlations between prolongation of coagulation brought about by the most active anticoagulants and inflammatory markers, and hence inflammatory state probably also contributed to the differences, as well as the mentioned differences in vitamin K levels. Conclusively, this paper suggests the suitability for controlling the effects of direct anticoagulants in DMT1 patients.