Background Anastomotic leak (AL) is one of the most important postoperative complications after hemicolectomy with stapled anastomosis. This study aimed to evaluate the association of preoperative vitamin D3 with early anastomotic leakage after right colon cancer surgery with stapled anastomosis. Method In this prospective cohort study, 535 patients who underwent right colon cancer surgery (right hemicolectomy) with stapled anastomosis were enrolled. A subset of 315 patients was included in the study after meeting the inclusion criteria. Preoperative vitamin D level was measured and analyzed for association with early AL using univariable and multivariable logistic regression analyses. Result This study included 315 cases; among them, 18 (5.71%) patients developed early AL. Vitamin D3 was significantly higher among patients without early AL ( P < .001). Low vitamin D3 status was reported among 111 patients (35.2%) and 204 (64.8%) of patients did not have low vitamin D3 status (sufficient level = 30-100 ng/mL). Sufficient vitamin D3 levels before right colon cancer surgery with stapled anastomosis was associated inversely with early AL (crude OR = .89, 95% CI = .85-.94, P < .001 and adjusted OR = .89, 95% CI = .82-.98, P = .02). Conclusion The vitamin D3 level has a protective association with early AL. As a result, low vitamin D3 status may be a risk factor for early AL development, suggesting that it can be one of the predictors of early AL occurrence.