Background: The objective of this study was to identify (1) the importance of a number of potential factors affecting the likelihood of sexual activity in perimenopausal women and (2) the likelihood of a number of barriers to sexual activity. Methods: A cohort of 780 women undergoing menopausal transition was surveyed annually for up to 7 years. Data were collected on sexual activity and, if not sexually active, reasons for no sexual activity, as well as a number of potential risk factors. Height and weight were measured at an annual clinic visit; serum hormone concentrations were assayed using blood samples donated annually. Data were examined with logistic regression models using the individual as a random effect, with subset analysis of nonsexually active women to determine the likelihood of each barrier. All factors with univariate associations of p < 0.1 were considered in multivariate model building with stepwise addition. Results: A total of 2440 woman-years were included in the analysis of sexual activity. The likelihood of sexual activity increased for women living with a partner, with perceived quality of life, and with less frequent hot flashes. Among 513 woman-years reporting no sexual activity, women living with a partner and women reporting frequent fatigue were less likely to lack a sexual partner, but were more likely to have sexual difficulties. Women with more physical work than average and women with higher serum estradiol levels were less likely to have sexual difficulties. Conclusions: The factors associated with sexual activity in menopausal women are complex, indicating that an individualized approach to improving sexual activity is required.