Purpose <p>Medullary thyroid cancer (MTC) is aggressive in nature compared with differentiated thyroid cancer, with a poor 10-year overall survival rate. Given the effect of the immune-inflammatory system on the survival of patients with cancer, the aim of this study was to investigate the prognostic significance of the preoperative Controlling Nutritional Status (CONUT) score in patients with MTC.</p> Methods <p>This multicenter, retrospective study included 221 patients with MTC who underwent thyroidectomy at four tertiary hospitals. The CONUT score was calculated for all patients using preoperative serum albumin and total cholesterol concentrations and lymphocyte counts. Patients were stratified into high and low CONUT score groups based on a cut-off score of 2.</p> Results <p>Overall, 164 (74%) and 57 (26%) patients were categorized into low and high CONUT score groups, respectively. There were no significant differences in the clinicopathological characteristics, including age, sex, primary tumor size, preoperative levels of calcitonin and carcinoembryonic antigen, and neck lymph node and distant metastasis between the two groups. The 10-year disease-specific survival rate in the high CONUT score group was significantly shorter than that in the low CONUT score group (85.7% <i>vs</i>. 97.3%; <i>p</i> &lt; 0.001). Multivariate analysis revealed that a high CONUT score was an independent prognostic factor for disease-specific survival (<i>p</i> = 0.008).</p> Conclusion <p>The preoperative CONUT score appears to be an independent prognostic indicator in patients with surgically treated MTC, with a high score indicating a poorer prognosis. Our findings underscore the importance of preoperative nutritional and immunological assessments in MTC management.</p> Graphical Abstract <p></p>