This research examines the relationship between urban polycentric spatial structure and driving. We identified 46 employment sub-centers in the Los Angeles Combined Statistical Area and calculated access to jobs that are within and beyond these sub-centers. To address potential endogeneity problems, we use access to historically important places and transportation infrastructure in the early 20th century as instrumental variables for job accessibility indices. Our Two-stage Tobit models show that access to jobs is negatively associated with household vehicle miles traveled in this region. Among various accessibility measures, access to jobs outside sub-centers has the largest elasticity (-0.155). We examine the location of places in the top quintile of access to non-centered jobs and find that those locations are often inner ring suburban developments, near the core of the urban area and not far from sub-centers, suggesting that strategies of infill development that fill in the gaps between sub-centers, rather than focusing on already accessible downtowns and large sub-centers, may be the best land use approach to reduce VMT.