This study examined interactive effects of sex and age on prefrontal brain anatomy in humans. It specifically targeted ranges of the adult life span and regions of cortex that previously showed male-female differences. Participants were 68 healthy human males and females aged 20-72 years. Data collection and analysis were conducted in parallel across two cohorts (laboratories) to investigate reproducibility of effects in relation to sex and age. Volumes for four regional prefrontal subfields per hemisphere were obtained from high-resolution MRI. Regional sex by age interactions were replicated across cohorts. In men, age effects were greatest in medial prefrontal volume, with decreases in dorsal medial and orbital medial regions. In women, age-related changes in medial prefrontal regions were limited to the dorsal volume, with additional decreases observed in lateral subfields. Cohort and Cohort x Age effects in total brain and total prefrontal volume were linked to a combination of methodological and sampling-related factors. Findings indicated that neuroanatomical changes throughout adulthood unfold along different time scales in men and women. Results also showed that sex differences in ageing localized to medial prefrontal regions were particularly robust to variation across cohorts.