The integrity of the bone-pin interface is the critical link in the stability of external fixation systems. External fixation pins placed in cancellous metaphyseal bone frequently loosen over time, resulting in fixation failure and an increased risk of infection. To design an external fixation pin with optimal bone-metal interface strength in cancellous bone, a systematic study of various thread design features was performed. Combinations of pitch, tooth profile, and minor diameter in 5 mm self-tapping half pins were evaluated in coaxial pullout testing using a fresh bovine cancellous bone. A significant increase in pullout strength was found with a decrease in minor diameter. No statistical differences were found in pullout strength attributable to thread profile and pitch. There were no significant interactions between minor diameter and tooth profile or minor diameter and pitch. The data obtained suggest significantly greater holding power in cancellous bone can be achieved by using an external fixation pin with a smaller minor diameter or a larger interference. Additional pullout testing of five commercially available external fixator pins was performed. Of these, the two pins with the largest interference demonstrated greater pullout strength. Therefore, within a range of acceptable major diameters and adequate minor diameters for the torsional strength requirements, an optimal interference for cancellous pin application may exist and it may well be larger than that present in currently available external fixation pins.