To assess the effects of a single 10% povidone iodine application as an adjunct to extensive surgical procedures in the clinical treatment of children with early childhood caries. Twenty-two children scheduled for dental treatment under general anesthesia were randomized into either an intervention group (10% povidone iodine), or a control group (phosphate buffered saline). Either povidone iodine or phosphate buffered saline was applied to teeth and soft tissues after prophylaxis and all operative dental procedures, followed by 1.23% acidulated phosphate fluoride gel. Saliva samples taken at baseline, and after 1 hour, 3 weeks and 3 months were assayed for mutans streptococci, lactobacilli and total viable bacteria. Caries lesions were recorded at baseline and at one year. Mutans streptococci and lactobacilli levels in the povidone iodine group were significantly reduced relative to baseline at 1 hour, 3 weeks and 3 months. At one year at least 60% of subjects had new caries lesions in each group, and there was no significant difference in caries increment between the two groups. Even prophylaxis, fluoride gel application and complete surgical treatment of caries at baseline were insufficient to prevent new caries in over 60% of the patients in these high caries risk infants. Although the one-time treatment with povidone iodine reduced mutans streptococci and lactobacilli levels for up to 3 months this therapy failed to additionally reduce future caries formation over one year, indicating that repeated antibacterial treatments will be needed to control high levels of cariogenic bacteria.