To improve local control, neoadjuvant radiotherapy (nRT) followed by surgery is the standard of care in myxofibrosarcoma (MFS) because of its infiltrative growth pattern. Nevertheless, local recurrence rates are high. Data on prognostic factors for poor clinical outcomes are lacking. This retrospective study thus investigates the prognostic relevance of magnetic resonance imaging (MRI) characteristics before and after nRT in 40 MFS patients, as well as their association with disease-free survival (DFS) and overall survival (OS). A vascular pedicle, defined as extra-tumoral vessels at the tumor periphery, was observed in 12 patients (30.0%) pre-nRT and remained present post-nRT in all cases. Patients with a vascular pedicle had worse DFS (HR 5.85; 95% CI 1.56–21.90; p = 0.009) and OS (HR 9.58; 95% CI 1.91–48.00; p = 0.006). An infiltrative growth pattern, referred to as a tail sign, was observed in 22 patients (55.0%) pre-nRT and in 19 patients (47.5%) post-nRT, and was associated with worse DFS post-nRT (HR 6.99; 95% CI 1.39–35.35; p = 0.019). The percentage of tumor necrosis estimated by MRI was increased post-nRT, but was not associated with survival outcomes. The presence of a tail sign or vascular pedicle on MRI could support the identification of patients at risk for poor clinical outcomes after nRT.