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Background: Use of postoperative radiation therapy (PORT) in locoregionally advanced medullary thyroid cancer (MTC) remains controversial. The objective was to evaluate the effect of PORT on locoregional control (LRC) and overall survival (OS). Methods: Retrospective cohort study of 346 MTC patients separated into PORT and no‐PORT cohorts. Relative indications for PORT, as well as changes in patterns of treatment, were recorded. Results: 49/346 (14%) received PORT. PORT was associated with worse OS; adjusted HR = 2.0 (95%CI 1.3–3.3). PORT was not associated with improved LRC, even when adjusting for advanced stage (Stage III p = 0.892; Stage IV p = 0.101). PORT and targeted therapy were not associated with improved OS compared to targeted therapy alone; adjusted HR = 1.2 (95%CI 0.3–4.1). Conclusions: Use of PORT in MTC has decreased and its indications have become more selective, coinciding with the advent of effective targeted therapies. Overall, PORT was not associated with improved LRC or OS. [ABSTRACT FROM AUTHOR]