Despite a number of studies on the efficacies of antiseptics for the prevention of blood culture contamination, it still remains unclear which antiseptic should be used. Although the combination of povidone-iodine and isopropyl alcohol has been traditionally used in many institutions, the application of povidone-iodine needs extra time, and there is little evidence that this combination could have an additive effect in reducing contamination rates. To elucidate the additive efficacy of povidone-iodine, we compared two antiseptics, 70% isopropyl alcohol only and 70% isopropyl alcohol plus povidone-iodine, in a prospective, nonrandomized, and partially blinded study in a community hospital in Japan between 1 October 2007 and 21 March 2008. All blood samples for culture were drawn by first-year residents who received formal training on collection techniques. Skin antisepsis was performed with 70% isopropyl alcohol plus povidone-iodine on all inpatient wards and with only 70% isopropyl alcohol in the emergency department. For the group of specimens from inpatient wards cultured, 13 (0.46%) of 2,797 cultures were considered contaminated. For the group of specimens from the emergency department cultured, 12 (0.42%) of 2,856 cultures were considered contaminated. There was no significant difference in the contamination rates between the two groups (relative risk, 0.90; 95% confidence interval, 0.41 to 1.98; P ؍ 0.80). In conclusion, the use of a single application of 70% isopropyl alcohol is a sufficient and a more cost-and time-effective method of obtaining blood samples for culture than the use of a combination of isopropyl alcohol and povidone-iodine. The extremely low contamination rates in both groups suggest that the type of antiseptic used may not be as important as the use of proper technique.The collection of blood samples for culture is essential for the diagnosis and management of patients with suspected bacteremia, and the importance of this practice has recently been reconfirmed in the Clinical and Laboratory Standards Institute's guideline Principles and Procedure for Blood Cultures in 2007 (5). However, the problem of false-positive results due to contamination has remained since the beginning of the use of modern techniques over 70 years ago. Contamination most commonly occurs when exogenous bacteria are inoculated into the culture medium from the patient's skin, the phlebotomist's hands, or phlebotomy kits. Contamination rates below 3% are generally considered acceptable (5, 9). Nevertheless, the reported rates of contamination vary from 0.8% to over 8% among institutions. Almost half of all positive results were reported to be contaminants at some institutions (1,4,15,18,20,23,24,26,31). With such a high contamination rate, it is not easy to interpret the results properly for clinicians. Consequently, contaminated blood cultures lead to extra costs because of the unnecessary use of antibiotics, prolonged hospitalization, and the subsequent possible development of antimicrobial resistance (3,15,23,25...