To investigate the role of autophagy in obese women’s impaired ability to undergo in vitro endometrial decidualization. Basic Science Project Women with regular menses, proven fertility and exclusion criteria of endometriosis were enrolled at the time of elective tubal ligation. Patients underwent an endometrial biopsy and each sample was cultured for nine days to synchronize the samples and plated into a control and decidualzed group. The decidualized group were exposed to 1 mM medroxyprogesterone acetate and 0.5 mM cAMP for nine days. The mRNA expression levels of prolactin (PRL) and Insulin Like Growth Factor Binding Protein 1 (IGFBP1) were measured by quantitative RT-PCR. The fold change in gene expression between control and decidualized samples was calculated. ATP assays were performed to assess the ATP activity in control and decidualized cells, transmission electron microscopy was performed for quantitation of autophagosomes in each group and Western blot analysis was performed measuring accumulation of microtubule-associated protein light chain 3 (LC3)-II and ubiquitin-binding protein p62 which together determines autophagic flux. Thirty-seven patients were included, twenty three obese patients and fourteen non-obese patients. Obese patients exhibited a statistically significant (p<0.05) decrease in gene expression fold change of both markers of endometrial decidualization. Similarly, the normally sustained decrease in ATP that occurs in control cell decidualization to trigger autophagy, occurred but was not sustained in obese patients (p<0.05). On TEM there were more autophagosomes in obese patients compared to non-obese suggesting that autophagy was initiated. Western immunoblotting revealed an increase in LC3-II in obese patients contributing to the fact that autophagy was initiated however there was a statistically significant increase in p62 in Obese patients (p<0.05) compared to non-obese suggesting that although autophagosomes are formed, there is an impairment in their function. Autophagy is a contributing mechanism in obese women’s impaired ability to undergo in vitro decidualization and this impairment is at the level of cargo recycling as evidenced by Western immunoblotting of p62 and not in initiation of autophagy as evidenced by TEM of autophagosomes and Western immunoblotting of LC3-II.