Background/Aims: Hemithyroidectomy is a common procedure for benign and low-risk thyroid lesions. Despite lower complication rates compared with total thyroidectomy, post-operative hypothyroidism and subsequent thyroxine requirement remain frequent. This study aimed to determine whether the ipsilateral nodule-to-lobe volume ratio (NLR) predicts thyroxine requirement following hemithyroidectomy. Methods: A retrospective cohort study was conducted of patients undergoing hemithyroidectomy between 2016–2024 across two sites in Melbourne, Australia. Hemithyroidectomy was defined as unilateral lobectomy with preservation of the contralateral lobe. Of 554 patients screened, 134 met inclusion criteria. Pre-operative ultrasound measurements (length, width, depth) were used to calculate nodule and lobe volumes, and NLR bands were derived (<25%, 25–50%, 50–75%, 75–100%). The primary endpoint was initiation of thyroxine within 12 months. Multivariable logistic regression assessed independent predictors; model discrimination was evaluated with ROC analysis. Results: Thyroxine was initiated in 29% of patients. Lower NLR (OR 0.18), higher pre-operative TSH (OR 2.98) and the presence of lymphocytic thyroiditis (OR 4.93) were independently associated with post-operative thyroxine requirement. Compared with NLR <25%, risk was lower across all higher-ratio bands. The multivariate model demonstrated good discrimination (AUC 0.79, 95%CI 0.69–0.89). Conclusions: Lower pre-operative NLR was associated with a higher likelihood of thyroxine requirement following hemithyroidectomy. When considered alongside established predictors such as pre-operative TSH and autoimmune thyroiditis, integrating NLR into pre-operative assessment may enhance counselling accuracy and refine individual risk stratification.