To investigate tooth-related factors that influence pocket closure (PC) and the reduction of pocket probing depths (PPD) after nonsurgical re-instrumentation (NSRI) as part of step 3 therapy. A total of 480 patients (10,807 teeth) presenting with residual pockets 6.33±3.79 months after steps 1 and 2 of periodontal therapy were included and retrospectively analyzed before and 5.93±4.31 months after NSRI. Reduction of PPD and PC rates following NSRI were associated with tooth-related factors, namely tooth type, arch, number of roots, furcation involvement (FI), pulp vitality, mobility, type of restoration, presence of plaque, and bleeding on probing (BOP), using mixed-effects regression models. NSRI reduced periodontal pockets persisting after initial cause-related therapy by (mean±SD) 1.32±1.79mm in PPD, and PC rate was 40%. Moderate pockets (4-5mm) responded better to NSRI than deep pockets (≥6mm) in terms of PC (51% vs. 16%). Both PPD reduction and PC rates of deep residual pockets were significantly influenced by tooth type, arch, number of roots, and presence of BOP. Tooth type, arch, number of roots, and presence of BOP at re-evaluation (before NSRI) had a significant and clinically relevant influence on NSRI as part of step 3 therapy. Considering these factors, particularly for deep residual pockets, may allow more tailored re-intervention. The present study aimed to investigate the influence of tooth-related factors on the outcome of repeated nonsurgical therapy of periodontitis. Therefore, 480 patients (10,807 teeth) presenting with clinical symptoms of persistent periodontitis after initial therapy were administered repeated nonsurgical therapy and retrospectively analyzed. Therapy outcomes were associated with tooth-related factors, namely tooth type, tooth location (maxilla/mandible), number of roots, involvement of the root furcation area in multi-rooted teeth, pulp vitality, mobility, restoration, presence of plaque and bleeding upon periodontal probing, using mixed-effects models. The results revealed that repeated nonsurgical therapy was effective in reducing inflammation and clinical signs of disease, with moderate residual periodontal defects responding better than deep defects. Healing of deep defects after repeated nonsurgical therapy; however, was significantly influenced by the factors: tooth type, location, number of roots, and bleeding on probing. Considering these factors, particularly in deep residual defects which are commonly suggested to be treated surgically, may allow less invasiveness and thus a more tailored re-intervention.