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Aim: Receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) have an established role in the pathogenesis of periodontitis, which is characterized by an increased RANKL/OPG ratio. The present study aims to investigate changes of RANKL, OPG and their relative ratio in gingival crevicular fluid (GCF) of periodontitis patients after non-surgical periodontal treatment. Materials and Methods: GCF was obtained from chronic periodontitis (n = 14), generalized aggressive periodontitis (G-AgP; n = 13) patients at baseline. The patients received scaling and root planing and were recalled after 2, 3 and 4 months for follow-up clinical examination and sampling. The total amounts and concentrations of RANKL and OPG in GCF were measured by enzyme-linked immunosorbent assay, and their relative ratio was calculated. Results: The RANKL/OPG ratio remained unchanged and did not correlate with clinical parameters throughout the monitoring period, despite the improved clinical outcome. This trend was similar in both chronic and G-AgP. Conclusions: Although the RANKL/OPG ratio has a potential diagnostic value for untreated periodontitis, it may not be a suitable predictor of clinically successful treatment outcome. As conventional therapy does not negatively modulate this ratio, the host could still be susceptible to further periodontal tissue destruction, warranting the consideration of adjunctive treatments. [ABSTRACT FROM AUTHOR]