Context: Evaluation of growth factor release from root canal dentin following conditioning with 17% ethylenediaminetetraacetic acid (EDTA) and 10% citric acid. Aim: To evaluate and compare the release of growth factors - transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF)-A, and platelet-derived growth factor (PDGF)-AB liberated from the root canal dentin after a final rinse with 17% EDTA and 10% citric acid, utilizing an enzyme-linked immunosorbent assay (ELISA). Methodology: One hundred and seventeen decoronated root canal cylinders were prepared from extracted single-rooted human teeth, and the root canal lumen was enlarged to a diameter of 1.3 mm, simulating an open apex. The prepared samples were divided into three groups based on the growth factors evaluated. Groups were further subcategorized into three subgroups depending on the final irrigant used, i.e., 17% EDTA, 10% Citric acid, and control Normal Saline. After final irrigation, the treated samples were placed in Eppendorf tubes prefilled with one mL of phosphate-buffered saline (PBS) and incubated at 37°C for 28 days. The amount of released growth factors in PBS solution was quantified using ELISA. Statistical Analysis: The data were analyzed using a one-way analysis of variance and Tukey post hoc test, performed with licensed GraphPad Prism (v5.0). Results: Ten percent citric acid and 17% EDTA significantly enhanced the growth factor release compared to normal saline. Ten percent citric acid demonstrated significantly greater efficiency than 17% EDTA in the release of growth factors. Release of TGF-β1 was highest among all the growth factors in the citric acid and EDTA-treated groups. VEGF-A release was significantly lower compared to TGF-β1 and PDGF-AB in the treated groups. Conclusion: Treatment of dentin with 17% EDTA and 10% citric acid significantly enhanced the release of all the growth factors, especially TGF-β1, with 10% citric acid being more effective compared to 17% EDTA.