ABSTRACTObjectiveWe investigated inbreeding effects on longevity and fertility in the House of Habsburg, one of the principal royal dynasties of Europe.MethodsA total number of 124 Habsburg marriages, involving 107 men and 124 women, in the period of approximately 1450–1800 were considered for the analysis. Kinship and inbreeding coefficients were computed from genealogical information, which included more than 8000 individuals.ResultsWe found a significant negative association between age of death and inbreeding coefficient (F) in those women who had children (regression coefficient b = −1.06, p = 0.0008). This result led us to investigate possible inbreeding effects on maternal mortality in the period of 4 weeks after the childbirth. A strong inbreeding depression on maternal survival was detected through the Kaplan–Meier curve for groups of women with different level of inbreeding (log‐rank test p = 0.0001) and the Cox proportional hazards regression analysis (hazard ratio = 2.36, p = 0.0008). Effect on fertility was also found as more inbred women had longer interbirth intervals (b = 154.66, p = 0.022). Effects of male or female inbreeding on the number of children per woman were not detected through zero‐inflated regression models suggesting that reproductive compensation might be occurring among the more inbred and less‐fecund women.ConclusionThe effect of inbreeding in adulthood in the Habsburg lineage was at least as important as that previously reported on prereproductive survival. To our knowledge, our results are the first evidence of an inbreeding effect on maternal mortality in humans.