Interfacial properties such as adhesion are determined by interfacial molecular structures. Adhesive interfaces in microelectronic packages that include organic polymers such as epoxy are susceptible to delamination during accelerated stress testing. Infrared-visible sum frequency generation vibrational spectroscopy (SFG) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) were used to study molecular structures at buried epoxy interfaces during hygrothermal aging to relate molecular structural changes at buried interfaces to decreases in macroscopic adhesion strength. SFG peaks associated with strongly hydrogen bonded water were detected at hydrophilic epoxy interfaces. Ordered interfacial water was also correlated to large decreases in interfacial adhesion strength that occurred as a result of hygrothermal aging, which suggests that water diffused to the interface and replaced original hydrogen bond networks. No water peaks were observed at hydrophobic epoxy interfaces, which was correlated with a much smaller decrease in adhesion strength from the same aging process. ATR-FTIR water signals observed in the epoxy bulk were mainly contributed by relatively weakly hydrogen bonded water molecules, which suggests that the bulk and interfacial water structure was different. Changes in interfacial methyl structures were observed regardless of the interfacial hydrophobicity which could be due to water acting as a plasticizer that restructured both the bulk and interfacial molecular structure. This research demonstrates that SFG studies of molecular structural changes at buried epoxy interfaces during hygrothermal aging can contribute to the understanding of moisture-induced failure mechanisms in electronic packages that contain organic adhesives. © 2013 American Chemical Society.