Costs of postexposure treatment of sharps injuries (SIs) in health care workers (HCWs) are an economic burden in many countries. This study analyzed the costs associated with SIs in HCWs in the Republic of Korea. Between October 1, 2005, and February 28, 2006, general information on SIs among HCWs and the direct costs (eg, laboratory, pharmacy, medical and surgical treatments) and indirect costs eg, (loss of working days) were collected prospectively from 34 hospitals nationwide. A total of 700 SIs were documented, 505 of which (72.1%) generated costs. The average costs per SI were pharmacy, 123,091 won (US$129); laboratory tests, 66,958 won ($70); medical services, 26,332 won ($28); and medical treatments, 9,377 won ($10). The average costs of preventive measures were 160,274 won ($168) for hepatitis B virus (HBV), 127,858 won ($134) for hepatitis C virus (HCV), and 139,552 won ($146) for HIV. Of the laboratory tests, 32.9% were HBV-related, 29.4% were HCV-related, and 19.8% were HIV-related. Of postexposure prophylaxes, 34.9% were HB immunoglobulin and 31.4% were HBV vaccines. We estimated that 7,057.5 SIs generated costs, at a total annual cost of 844,587,577 won ($884,385). The direct costs of managing SIs among HCWs constitute an economic burden in Korea. More aggressive and comprehensive preventive measures of SIs should be adopted.