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Unexplained infertility (UI) represents about 25-30% of all known types of female infertility. To date, UI remains an unsolved problem in a subgroup of infertile but otherwise healthy women and the molecular causes of UI are not yet known. In the current study, we have compared and analyzed the proteomic profile of receptive phase (LH+7) endometrium from fertile and infertile women, with a view to identify the appropriate protein target signatures that may be responsible for defective endometrial receptivity as a cause of UI. 12 Differentially expressed proteins (8 up-regulated and 4 down-regulated) were identified by Liquid Chromatography-Mass Spectrometric analysis. These differentially expressed proteins were involved in immunological response, glycolytic pathway, lipid metabolism, blood agglutination, protein synthesis, molecular chaperone, antioxidant system, mitochondrial ATP generation, and Ca+2 signalling. The expression of four differentially expressed proteins such as HSPβ-1, Apolipoprotein-A1, IGK@ protein, and RPLP2 were further validated by immunoblotting and immuno-histochemical analysis in separate biopsy samples, and also in in-vitro experimental model of decidualization of human endometrial stromal cells (hESCs). This study explored several proteins that may have functional significance as regards the initiation and maintenance of the window of receptivity. Results of this study might be helpful in understanding the molecular basis of endometrial defects in a subset of infertile women having normal ovulation and hormonal profile. To our understanding, this is the first study to demonstrate the differential endometrial protein profiling in women with endometrium basedunexplained infertility.