Background This study compared survival between patients who had medullary thyroid cancer (MTC) treated with surgery alone and patients who underwent surgery and radiation (SRT). Methods Patients from the National Cancer Database (NCDB) with a diagnosis of stage 3 or 4 MTC, lymph node disease, and no distant metastases between 2008 and 2016 were studied. Kaplan–Meier analyses and log-rank statistics were used to estimate and compare overall survival between patients treated with surgery alone and those treated with SRT. Mutlivariable Cox proportional hazards models and propensity-matching were used to adjust for confounding and selection bias. Results Among 1370 patients, 1112 (81%) received surgery alone, and 258 (19%) received SRT. The hazard ratio for mortality in the SRT group was 1.784 (95% confidence interval CI 1.313–2.43) after multivariable adjustment for confounding variables. Furthermore, SRT remained associated with a higher mortality rate ( p  < 0.008) after propensity-matching in an effort to adjust for selection bias. Conclusions This analysis of NCDB patients showed that SRT is associated with a significantly higher mortality rate among patients treated for stage 3 or 4 IV MTC with positive lymph node disease. Although this observation can be attributed to unmeasured confounders or selection bias, the cause for the profound survival differences deserves prospective evaluation, especially as adjuvant therapies for this disease continue to evolve.