While antithrombotics are usually administered intravenously, subcutaneously or orally, there are a number of publications reporting topical application of anticoagulation therapy. This paper aims to review the available literature regarding clinical conditions, the details of the topical antithrombotic treatment, as well as positive or adverse effects in an attempt to ascertain the safety and efficacy of this form of treatment. Published literature was searched to identify publications reporting the use of antithrombotic treatments administered via topical application between 1st January 1990 and 1st January 2013. There were 43 studies reported in 10 different clinical conditions. Majority of the studies were randomized controlled trials (51.2%), prospective studies (18.6%) or case reports (11.6%). The clinical conditions in which topical antithrombotics were administered included: microangiopathy, acute haemorrhoids, periodontitis, dermatitis, burns, ocular conditions and surgery, blunt force impact, scars, as well as clinical conditions associated with superficial venous thrombosis (SVT). The most commonly used topical antithrombotic was heparin (79.1% of studies). The respective dosage of different antithrombotics varied depending on specific clinical conditions. While most studies reported mean improvements or resolution of symptoms/condition in patients, the patient outcomes were variable. This review demonstrates that topical antithrombotic treatment is used according to a wide variety of protocols, with a subsequent variability in patient outcomes. Specific guidelines for the use of topical antithrombotics should be developed to standardize this form of treatment and ensure the best possible outcomes for patients.