To provide guidance for future light water reactor core design and fuel management strategies, the effects of the moderator-to-fuel ratio on burnup, core endurance, and waste disposal characteristics have been investigated. The analysis is based on a unit cell model of the standard four-loop Westinghouse pressurized water reactor (PWR) with varied water density, rod diameter, and lattice pitch. Two state-of-the-art computer codes, CASMO-4 and MOCUP (MCNP+ORIGEN), have been used. Considering the entire range of moderation (from fast spectra to overthermalized spectra), the results show that higher reactivity-limited burnup is achievable by either a wetter lattice or a much drier lattice than normal. In particular, epithermal lattices are distinctly inferior performers. Current PWR lattices are about the optimum in terms of highest fuel endurance. However, wetter lattices produce less plutonium with a degraded plutonium isotopic mix with respect to weapons usability. Neptunium-237 content is only mildly affected by the hydrogen-to-heavy-metal ratio. High burnup is significantly beneficial to reducing plutonium production per unit energy and to making its isotopic mix less attractive as a weapon material. In particular, the 238Pu to 239Pu ratio increases approximately as the 2.5 power of burnup for a fixed initial enrichment. Based on this neutronics study, wetter lattices are recommended for future high-burnup applications.