Significant decreases in both male and female fertility have been observed over the past 50 years, with female conceptions rates dropping by 44% and male sperm counts decreasing by over 50%. This dramatic decrease in fertility can be attributed in part to our increasing exposure to endocrine disrupting chemicals (EDCs). Diethylstilbestrol (DES) is an estrogenic EDC that was prescribed to millions of pregnant women between 1940-1970 and resulted in reproductive defects in the offspring that were exposed in utero. Women who were exposed to DES in utero experienced higher rates of infertility, pregnancy complications and reproductive cancers. Alarmingly, there is evidence to suggest that these effects may persist in the grandchildren and great grandchildren of exposed women. To define the transgenerational reproductive impacts in females following exposure to DES, gestating F0 female mice were exposed to 1, 50 or 100ug/kg of DES. The effects of DES were monitored in the F1-F4 female descendants. Reductions in pregnancy rate and fertility index were observed up until the third generation and the onset of puberty was significantly affected, with the timing of vaginal opening occurring significantly earlier in DES descendants. The anogenital distance (AGD) was also impacted in DES descendants with all concentrations resulting in a significantly smaller AGD up until the third, unexposed generation. Furthermore, alterations to the reproductive tract were also observed, with DES descendants presenting higher rates of urethral-vaginal fistulae. These results indicate a transgenerational effect of DES on multiple reproductive parameters including fertility, timing of puberty, AGD and reproductive tract development. These data have significant implications for the >50 million DES descendants worldwide as well as raising concerns for the ongoing health impacts caused by exposures to other estrogenic EDCs which are pervasive in our environment.