This study was designed to assess the risk of hematoma related to the combination of peripheral nerve blocks and thromboprophylaxis. A total of 3588 patients undergoing joint arthroplasty were included. Blocks performed included continuous lumbar plexus, continuous femoral, and continuous or single sciatic. The perineural catheters were removed on postoperative days 2 or 3. A total of 6935 blocks were performed in patients receiving warfarin (50.0%), fondaparinux (12.8%), deltaparin (11.6%), enoxaparin (1.8%), and aspirin (23.8%). In this patient population, no perineural hematoma was recorded. Our data provide evidence that continuous/single peripheral nerve blocks can be safely performed before thromboprophylaxis initiation, and perineural catheters can be safely removed while the patient is receiving thromboprophylaxis and/or aspirin.