Objective To investigate the diagnostic value of BRAF ^V600E gene mutation, ultrasonographic features, and body mass index (BMI) in distinguishing benign from malignant thyroid nodules classified as TI-RADS category 3 or higher. Methods A retrospective analysis was conducted on 203 patients with TI-RADS category 3 or higher nodules who were diagnosed and treated at the Chaohu Hospital Affiliated to Anhui Medical University from October 2022 to December 2023. The specificity, sensitivity, and other diagnostic indicators of different diagnostic methods were compared. Logistic regression analysis was employed to identify risk factors for malignant nodules. Results The malignant group exhibited a higher proportion of features on ultrasonography (e.g., hypoechoicity, solid composition, ill-defined margins), a higher BMI, and a greater rate of BRAF ^V600E mutation compared to the benign group (P<0.05). The combination of all three examinations demonstrated superior sensitivity (74.2%), negative predictive value (88.8%), and overall diagnostic efficacy (0.821) compared to any single method alone (P<0.05). Logistic regression analysis identified a BMI ≥ 28 kg·m ^-², hypoechoicity, capsular invasion, and BRAF ^V600E mutation as significant risk factors for malignant nodules (P<0.05). Conclusion The combination of BRAF ^V600E gene mutation analysis, ultrasonographic characteristics, and BMI demonstrates clinical value in differentiating benign from malignant thyroid nodules classified as TI-RADS category 3 or higher.