Over the past decade, a variety of advanced silver-based dressings have been developed. There are considerable variations in the structure, composition, and silver content of these new preparations. In the present study, we examined five commercially available silver-based dressings (Acticoat, Aquacel Ag, Contreet Foam, PolyMem Silver, Urgotul SSD). We assessed their cytotoxicity in a monolayer cell culture, a tissue explant culture model, and a mouse excisional wound model. The results showed that Acticoat, Aquacel Ag, and Contreet Foam, when pretreated with specific solutes, were likely to produce the most significant cytotoxic effects on both cultured keratinocytes and fibroblasts, while PolyMem Silver and Urgotul SSD demonstrated the least cytotoxicity. The cytotoxicity correlated with the silver released from the dressings as measured by silver concentration in the culture medium. In the tissue explant culture model, in which the epidermal cell proliferation was evaluated, all silver dressings resulted in a significant delay of reepithelialization. In the mouse excisional wound model, Acticoat and Contreet Foam indicated a strong inhibition of wound reepithelialization on the postwounding-day 7. These findings may, in part, explain the clinical observations of delayed wound healing or inhibition of wound epithelialization after the use of certain topical silver dressings. Caution should be exercised in using silver-based dressings in clean superficial wounds such as donor sites and superficial burns and also when cultured cells are being applied to wounds.