To compare the intrinsic stability of two distal interlocking screw orientations for tibial nailing of distal third tibial diaphyseal fractures without isthmal support, six Depuy (Warsaw, Indiana) tibial intramedullary nails were implanted in simulated distal tibiae. The constructs received both two parallel (medial to lateral) and two perpendicular (one medial to lateral, one anterior to posterior) distal interlocking screws in a random order Angular, translational, and torsional displacements of the nails were measured in response to 70 N proximal applications of anterior, posterior, medial, and lateral loads, and a 7.7 Newton-meter torsional load. There were no differences in medial or lateral angulations between the screw orientations (average: 2.5 degrees, p > 0.8). Angulation in the sagittal plane (anterior and posterior) was slightly less for parallel screw fixation (1.6 degrees versus 2.4 degrees), but this was not statistically significant (p > 0.1). Rotational angulation was higher in the parallel (average: 9.9 degrees) versus the perpendicular (average: 8.1 degrees) screw orientation, but these results were not statistically significant (p > 0.1). Pure translation did not occur in either the parallel or perpendicular screw orientations. These results indicate that fixation stability of these tibial intramedullary nails is not significantly influenced by distal interlocking screw orientation in response to sagittal, coronal, or rotational forces.