In the second half of the 19th century, the study of blood physiology became one of the leading experimental areas, whose relevance had been associated not only with the emergence of new research methods, but also with the growing popularity of blood transfusion in clinical practice. However, the widespread use of the blood transfusion practice was impossible without solving the problem of thrombosis. Patient safety required a detailed study of the causes of blood clotting and the search for effective methods to overcome it. A comprehensive understanding of this process was proposed by the University of Dorpat professor Alexander Schmidt, who created the enzymatic theory of thrombosis, and his students (Jakovitsky, Sachsendahl, Köhler, Birk and others), studied the formation, content and action of the fibrin enzyme in a living organism. They managed to prove the multistage nature of the blood coagulation process, to explain the mechanism of its internal regulation in a living organism and to describe the pathology of blood transfusion. Studying the contribution of Schmidt’s scientific school to improving scientific ideas about the mechanism of coagulation, the safety of blood transfusion and the methodology of experimental physiological research in general became the purpose of this article.