Abstract Introduction: Angiogenesis, the generation of new vessels, is regulated by several growth factors. The most important of them is vascular endothelial growth factor (VEGF), which is closely related to tumor progression and prognosis. To my knowledge no study in sub-Saharan Africa has evaluated the level of VEGF following surgery in African patients. This study therefore aims to evaluate the pattern and clinical implication of VEGF expression in benign and malignant neoplasms and determine the effect of surgical intervention on the levels of circulating VEGF. Methods: This case-control study was carried out at the University of Benin Teaching Hospital (UBTH), Benin City, Nigeria, between October 2015 and February 2017. Cases were drawn from among histologically confirmed orofacial tumors, while controls were from consecutive, ambulatory dental patients, matched for age and sex. Calculated sample size for minimum effect was 77 for both cases and controls. Blood samples were taken from cases and controls, pre- and 1-month post-surgery, allowed to clot and serum aliquots were stored at -600 C till analyses. Post-surgery tissue was processed and stained with anti-VEGF antibody for immunohistochemical analysis. Serum VEGF was analyzed using Sandwich ELISA, and mean levels as well as median were measured. Spearman correlation was estimated, t-test measured significance (at p ≤ 0.05), and one-way ANOVA measured between group differences. Results: Following 12% attrition, 81 subjects were retained in the study (55 cases [20 malignant, 35 benign] and 26 controls). The most common malignant neoplasms were head and neck squamous cell carcinoma (35%) and polymorphous low-grade adenocarcinoma (20%), while the benign tumors were mostly unicystic ameloblastoma (42.9%) and solid multicystic ameloblastoma (31.4%). Before surgical treatment, there were significantly different serum levels of VEGF in benign (48.11 ± 25.19 pg/ml) vs. malignant cases (1065.00 ± 412.14 pg/ml), and compared with controls (45.42 ± 29.83 pg/ml), p <0.001. Also, the level of circulating VEGF correlated strongly and positively with tumor tissue expression in malignant cases (r = 0.674, p <0.001). After definitive surgical intervention, there was a significant reduction in the level of serum VEGF in both benign (45.50 ± 24.71 pg/mL) and malignant cases (51.22 ± 16.84 pg/mL), p <0.001. One-way ANOVA revealed no significant differences between cases and controls post-surgery. Conclusion: There were elevated levels of serum VEGF in benign and malignant orofacial neoplasia, which correlate positively with the expression of VEGF in tumor tissue. Surgery caused a significant reduction of circulating VEGF to normal levels irrespective of age, gender, previous medical history, perceived duration of the lesion and lymph node involvement. Citation Format: Aimuamwosa Obarisiagbon, Peter Egbor, Ozoemene Ndubuisi Obuekwe, Osagie Akpata, Akin Ojo, Nosayaba Osazuwa-Peters. Does surgical treatment affect serum levels of vascular endothelial growth factor (VEGF) in orofacial tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1556.