Thrombosis is defined as a necessary physiological clotting process of hemostasis or harmful clinical events manifested as acute myocardial infarction (AMI), acute coronary syndromes (ACS), and thrombotic diseases. Nowadays, thrombotic diseases are the leading causes of morbidity and mortality which incur substantial healthcare expenditures worldwide. There are some shortcomings for current antithrombotics including bleeding potential, unpredictable pharmacokinetic and pharmacodynamic profiles, limited reversibility, and so on. Aptamers are short RNA or single-stranded DNA (ssDNA) oligonucleotides that fold into 3D conformations to recognize and bind their cognate targets. Aptamers are selected by an in vitro selection technique, i.e., Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Chemical synthesis renders aptamers both the characteristics of small molecule drugs and those of monoclonal antibodies. Some additional unique features, such as high specificity and affinity, flexible modification and stability, and lack of toxicity and immunogenicity, make aptamers hold great potential as a novel class of drugs and diagnostic reagents. In this review, we focus on the development of several aptamers and in particular those aptamers that have entered into clinical trials against anticoagulation factors and anti-adhesion molecules which are potential antithrombotics for thrombotic diseases.