Background: Hypoxia-inducible angiogenic pathway involving hypoxia inducible factor-1 alpha (HIF-1), vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-) may regulate several biological processes related to inflammation. The present study aimed to assess the effect of non-surgical periodontal treatment on gingival crevicular fluid (GCF) HIF-1 , VEGF, and TNFlevels in generalized aggressive periodontitis (G-AgP). Methods: Twenty G-AgP patients and 20 periodontally healthy individuals were included. G-AgP patients received scaling and root planning (SRP), per quadrant at a 1-week-interval, performed with ultrasonic and periodontal hand instruments. GCF samples were collected and clinical periodontal parameters including probing depth, clinical attachment level, gingival index and plaque index were recorded at baseline, 1 and 3 months after treatment. Biomarker levels in GCF were analyzed by ELISA. Results: At baseline all clinical parameters and GCF HIF-1 , VEGF, and TNFlevels were significantly higher in G-AgP patients compared to healthy control (P < 0.05). All clinical parameters improved over the 3-month-period in G-AgP patients (P < 0.05). GCF HIF-1 levels in G-AgP reduced at 1 and 3 months posttreatment, however, this did not reach to statistical significance (P > 0.05). GCF VEGF and TNF-levels remained unchanged throughout the study period (P > 0.05). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.