Purpose: Menstrual-cycle irregularity may have an important influence on the subsequent development of chronic diseases. Several risk factors for irregular menstrual cycles have been detected, including stress. Our aim was to extend research on the link between chronic stress and menstrual-cycle irregularity and to assess potential protective factors, such as dispositional resilience, which we hypothesize to be associated with the maintenance or promotion of a healthy menstrual cycle. Methods: For this cross-sectional study, data on 696 healthy women aged 20-40 years were obtained. The women completed measures of chronic stress, dispositional resilience and menstrual-cycle irregularity. Furthermore, potential confounds were assessed. Results: Of the participants, 383 (55%) reported no current use of hormonal contraceptives; 313 (45%) reported current use hormonal contraception and were included as a control group. The results suggest that in women not using hormonal contraception, chronic stress (OR = 1.05, 95% CI = 1.02-1.08, p = 0.001) and dispositional resilience (OR = 0.43, 95% CI = 0.31-0.59, p<0.001) have a main effect on menstrual cycle regularity. In addition, women with greater dispositional resilience have reduced risk for irregular menstrual cycles in the face of low to moderate chronic stress; however, this association is changed at the highest level of chronic stress. Conclusions: These findings suggest that dispositional resilience may be a protective psychological trait that modulates reproductive functioning.