Antithrombotic agents play important roles in the prophylactic and therapeutic management of many cardiovascular disorders. Therefore, many researchers have focused on developing new strategies for anticoagulation. New oral anticoagulants and factor Xa inhibitors are products of such research. Although they are identified as advantageous, there are limited data available about their multisystemic interactions. Thus, the antiangiogenic behaviors of oral factor Xa inhibitors and low molecular weight heparins (LMWHs) were investigated in this study. The chick chorioallantoic membrane (CAM) model was designed to investigate the antiangiogenic potential of new oral factor Xa inhibitors (rivaroxaban) and LMWHs (enoxaparin sodium and tinzaparin sodium). Four different molar concentrations (10−4, 10−5, 10−6, and 10−7 μmol/l) were studied for each drug. Each concentration was studied on 20 fertilized eggs. Vessel structures were evaluated under a stereoscopic microscope, and vessel formation was scaled according to previous literature. Both enoxaparin and tinzaparin sodium have increased antiangiogenic efficacy on CAM in a dose-dependent manner. However, this increased efficacy did not reach significant levels (average score < 0.5). On the contrary, while rivaroxaban showed dose-dependent antiangiogenic properties similar to enoxaparin and tinzaparin, a significant average antiangiogenic score (0.7) was detected at 10−4 μmol/l concentrations. New oral anticoagulants seem to be more favorable. However, their safety for the cardiovascular system needs to be clarified through microsystem studies on, for example, angiogenesis.