Earthquakes often occur on faults that juxtapose different rocks. The result is rupture behavior that differs from that of an earthquake occurring on a fault in a homogeneous material. Previous 2D numerical simulations have studied simple cases of earthquake rupture propagation where there is a material contrast across a fault and have come to two different conclusions: 1) earthquake rupture propagation direction can be predicted from the material contrast, and 2) earthquake rupture propagation direction cannot be predicted from the material contrast. In this paper we provide observational evidence from 70 years of earthquakes at Parkfield, CA, and new 3D numerical simulations. Both the observations and the numerical simulations demonstrate that earthquake rupture propagation direction is unlikely to be predictable on the basis of a material contrast.