ABSTRACT: The aim of this two-year cohort study was to investigate salivary microRNAs (miRNAs) that predict periodontitis progression. A total of 120 patients who underwent supportive periodontal therapy were recruited. Unstimulated whole saliva was collected at baseline. Two years later, 44 patients were followed up (median age, 67.1 years) and divided into two groups: progression group (n = 22), with one or more sites with clinical attachment level (CAL) progression (>3 mm compared with baseline) or tooth extraction due to periodontitis progression; and the control group (n = 22), which did not exhibit CAL progression. In the microarray analysis of salivary miRNAs, hsa-miR-5571-5p, hsa-miR-17-3p, hsa-let-7f-5p, hsa-miR-4724-3p, hsa-miR-99a-5p, hsa-miR-200a-3p, hsa-miR-28-5p, hsa-miR-320d, and hsa-miR-31-5p showed fold change values <0.5 or ≥2.0 in the progression group compared with the control group (p < 0.05). On receiver operating characteristic curve analysis, areas under the curves of hsa-miR-5571-5p, hsa-let-7f-5p, hsa-miR-99a-5p, hsa-miR-28-5p, and hsa-miR-320d were >0.7, indicating fair discrimination power. The expressions of salivary hsa-miR-5571-5p, hsa-let-7f-5p, hsa-miR-99a-5p, hsa-miR-28-5p, and hsa-miR-320d were associated with periodontitis progression in patients with chronic periodontitis. These salivary miRNAs may be new biomarkers for progression of periodontitis, and monitoring them may contribute to new diagnostics and precision medicine for periodontitis.