Povidone-iodine (PVP-I) possesses broad-spectrum antimicrobial activity and is used clinically as a disinfectant. We evaluated the disinfectant properties and safety of PVP-I for use as a contact lens solution. The concentrations of PVP-I required to reduce the number of Staphylococcus aureus or Candida albicans by 3 log units were lower than were those of hydrogen peroxide, polyhexamethylene biguanide (PHMB), and benzalkonium chloride (BAK). The cytotoxicity of PVP-I for cultured human corneal epithelial (HCE) cells was less than that of the other three agents. The safety margin for PVP-I was thus greatest among the tested compounds. PVP-I appears suited for use as a contact lens disinfectant.