Desert mule deer (Odocoileus hemionus eremicus) in central Arizona declined from 11 deer/km² in the early 1960s to 2 deer/km² in 2006. We had the opportunity to examine the causes of desert mule deer population fluctuations in Arizona from 1960 to 2006 by contrasting deer density, body condition, productivity, and diet quality inside and outside of the 259-ha Walnut Canyon Predator Proof Enclosure (WCPPE) on the Three Bar Wildlife Area (TBWA) in central Arizona. Mule deer inside the enclosure increased from 11/km² in 1997 to 32 deer/km² in 2004 while mule deer outside the enclosure in the TBWA remained between 1 and 5 deer/km² during the same time. There was no difference in body mass and number of fetuses (in utero) between mule deer inside and outside the enclosure. However, there was evidence of mule deer in better body condition inside the enclosure compared to mule deer outside the enclosure. Mule deer inside the enclosure consumed a diet higher in energy than mule deer outside the enclosure. There were no differences in plant species diversity or composition inside and outside the enclosure. Current mule deer densities in the study area are below what the environment is capable of maintaining, and a history of higher mule deer densities inside WCPPE over 40 y has not resulted in measurable impacts on the highly diverse plant communities of TBWA. Observed differences in diet quality of mule deer may be related to trade-offs incurred through predation risk, where mule deer inside the enclosure are maximizing their energy intake without the burden of predator avoidance and vigilance. Our study provided evidence that current mule deer densities in central Arizona are below what the environment is capable of sustaining.