The results of a 23-year study of caloric restriction in rhesus macaques are reported; restricted caloric intake did not increase survival, but improved the metabolic profile of monkeys started at older ages and showed a trend towards delaying age-associated disease in monkeys started at a young age. Restricting food intake has been shown to extend lifespan and improve health in various species. Here, the results of a 23-year study of caloric restriction in rhesus macaque monkeys are reported. When started at older ages, restricting caloric intake did not increase survival, but improved the metabolic profile of the monkeys. Young monkeys on a calorie-restricted diet showed a trend towards a delay in age-associated disease onset, but they, too, showed no increase in lifespan. Given that lifespan studies in humans are impractical, work with non-human primates is as near as we can get, and these results suggest that the effects of caloric restriction in long-lived animals are far from straightforward. Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function1,2, motor coordination3 and resistance to sarcopenia4 in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years)5 and a preliminary report with a small number of CR monkeys6. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents7,8,9, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.