Epigallocathechin gallate (EGCG) possesses many beneficial properties, such as anticarcinogenicity, antiatherogenicity, as well as antioxidant and antibacterial activities. However, the bacterial response to sublethal concentrations of EGCG has not been studied. Here we investigated whether short exposure of staphylococci strains to sublethal doses of EGCG can lead to adaptation and cross-resistance. Two-hour exposure of five strains to 20µg/ml of EGCG did not affect the growth rate but significantly elevated the resistance towards antibiotics targeting the bacterial cell wall. The magnitude of cross-resistance towards such antibiotics varied with the staphylococci strain, with Staphylococcus aureus Newman exhibiting the highest magnitude of cross-resistance, showing a 2, 4 and 8-fold increase in resistance towards vancomycin, oxacillin and ampicillin respectively. All EGCG-adapted strains were also more heat tolerant than their control counterparts as derived from the Weibull model. Adaptation to EGCG led to a moderate increase in heat resistance of the adapted strains S. epidermis ATCC 12228, S. aureus Newman, and S. aureus ATCC 29213, and an extremely pronounced increase for S. aureus ATCC 6538 and S. aureus RN4220. The shape of the survival curve also varied with the staphylococci strain. Transmission electron microscopy (TEM) analysis revealed suppressed separation of daughter cells in cultures exposed to EGCG, as evidenced by the pseudomulticellular appearance and by more than 2-fold increase in cell wall thickness. These observations raise concerns over the potential of EGCG utilization in therapy in that it may contribute to the development and enhancement of microbial resistance mechanisms.