Background: While current clinically administered anticoagulant medications have demonstrated effectiveness, they have also precipitated significant risks: severe bleeding complications including, but not limited to, gastrointestinal hemorrhaging and intracranial and other life-threatening major bleedings. An ongoing effort is being made to identify the best targets for anticoagulant-targeted drugs. Coagulation factor XIa (FXIa) is emerging as an important target of current anticoagulant treatment. Objective: This review will summarize the development of anticoagulants and recent advances in clinical trials of experimental factor XI inhibitors from a clinical application perspective. Results: As of 1 January 2023, our search screening included 33 clinical trials. We summarized the research progress of FXIa inhibitors from seven clinical trials that evaluated their efficacy and safety. The results showed no statistically meaningful distinction in the primary efficacy between patients receiving FXIa inhibitors compared to controls (RR = 0.796; 95% CI: 0.606–1.046; I2= 68%). The outcomes did not indicate a statistical difference in the occurrence of any bleeding between patients receiving FXIa inhibitors compared to controls (RR = 0.717; 95% CI: 0.502–1.023; I2= 60%). A subgroup analysis found significant differences in severe bleeding and clinically relevant hemorrhaging in subjects receiving FXIa inhibitors compared to Enoxaparin (RR = 0.457; 95% CI: 0.256–0.816; I2= 0%). Conclusions: Clinical trials to date have indicated that factor XIa is a potential anticoagulation target, and factor XIa inhibitors may play an important role in the development of anticoagulants.