Major orthopaedic surgeries have higher risk in terms of venous thromboembolism (VTE). All current guidelines recommend VTE prophylaxis to prevent postoperative complications. Although, there is not a concensus, there are multiple agents and regimes discussed in current literature. In this review, we aimed to discuss currently available VTE prophylaxis agents, in terms of mechanism, usage, dosing, possible toxicity, and available antidots. To have an optimum prophylaxis and before making a decision, surgeon should consider patient spesific factors, and update his/her literature knowledge.