Objectives: Polyvinylpyrrolidone-iodine (PVP-iodine or povidone- iodine) enhances the treatment outcomes of initial periodontal treatment but the degree of benefit varies in the literature. A main reason might be the concentration of the dosage form and its contact time with the periodontal tissues. In this randomized pilot study the effect of repeated subgingival application of PVP-iodine during scaling and root planing (SRP) was assessed. Changes of clinical parameters and microbiotic taxa after 3 months were analyzed. Method and Materials: In a split-mouth design 12 patients with generalized, severe periodontitis were treated with SRP combined with subgingival application of either PVP-iodine or water. Test and control sides were isolated with a special rubber dam technique. Irrigations were reapplied during SRP. Periodontal probing depth (PD) and recessions were documented before treatment and after 3 months. Samples of subgingival bacteria before SRP and after 1 week, 1 month, and 3 months were analyzed. Results: Three months after SRP, changes for PD and recession in deep pockets were significantly higher in the PVP-iodine group (P = .012 and .044 respectively). The number of these pockets was reduced from 73 at baseline to 8 in the test and 19 in the control group. In both groups, bacterial taxa were reduced after 1 week. One month after SRP only taxa of Porphyromonas gingivalis in the PVP-iodine group were lower than at baseline. After 3 months, all taxa regained baseline values. Conclusion: PVP-iodine reapplied frequently during SRP might enhance pocket depth reduction in initially deep pockets. Keywords: microbiology, nonsurgical periodontal therapy, periodontitis, povidone-iodine