To determine if iodine tincture is a more effective skin antiseptic for blood culture collection than povidone-iodine, an iodophor. Pairwise comparisons across phases. In phases 1 and 3, blood culture skin preparation was performed with the iodophor; in phases 2 and 4, skin preparation was performed with iodine tincture. Emergency department of a large urban teaching hospital. All adult patients seen in the emergency department who had blood cultures collected because a systemic bacterial infection was suspected. The blood culture contamination rate for the iodophor and iodine tincture skin preparations. A total of 8467 blood cultures were collected during the study, and 421 (4.97%) were classified as contaminated. The contamination rate for the blood cultures collected using the iodophor was 6.25%, and the contamination rate for the cultures using iodine tincture was 3.74%; this difference is statistically significant (P < .00001). The effectiveness of the skin antiseptic may be an important factor in determining contamination rate in blood culturing. If these results are confirmed by others, then institutions that have a high blood culture contamination rate when using an iodophor for skin preparation should consider changing to iodine tincture.