Intramedullary nailing of shaft fractures of the femur and tibia is a recognized operative procedure and its use has even been enlarged by the introduction of the so-called interlocking technique. In recent years case reports have been published describing peroperative pulmonary embolism during reamed femoral nailing, suggesting either an unfavorable effect of the reaming or the pressure increase in the medullary cavity while reaming and nailing. In an in vitro study on explanted human femora and tibiae we investigated the intramedullary pressure increase in reamed and unreamed nailing procedures of both bones. A lower pressure increase was noted in unreamed nailing compared to reamed nailing in the femur (289/496 mm Hg) and in the tibia (128/>833 mm Hg). The unreamed tibial nailing displayed significantly less pressure increase than the unreamed femoral nailing (p = 0.01). Opening of the medullary cavity with the so-called cheese cutter (cannulated cutter over a centering pin) showed significantly greater pressure increase in the femur than in the tibia (p = 0.01). Pressure increase seems to be dependent of the mode of insertion of the unreamed nail (ram-blows versus manual insertion), although the difference in the tibial unreamed nailing is statistically not significant.