The generation of intramedullary pressure during nailing of the femur and the tibia using reamed and unreamed nailing techniques was investigated and compared in an in vitro study in intact, cadaveric human bones. The pressure was assessed by distal supracondylar measurements via a small hole in the metaphyseal cortex. No significant difference in the intramedullary pressure increase was seen in the femur whether a reamed or unreamed nailing technique was used in contrast to the tibia (p = 0.01). A distal venting hole in the femur did not lower the increase in pressure during insertion of an unreamed nail. Using the cannulated cutter to open the medullary canal showed a significant increase in pressure compared to the use of the awl in the femur (p = 0.01), but not in the tibia.