Soft tissue sarcomas of the extremities or trunk are often resected after treatment with neoadjuvant radiotherapy. Adequate surgical resection margins for sarcomas after neoadjuvant cytotoxic therapy are not well characterized. Minimum surgical resection margins required for local control of primary, high-grade, pleomorphic soft tissue sarcomas treated with neoadjuvant therapy was assessed by competing risk regression in a series of 166 cases. Optimal tumor clearance was determined to be ≥1 mm. Predictive accuracy of three commonly used resection margin classification schemes (American Joint Committee on Cancer, Musculoskeletal Tumor Society, and the margin distance method) were comparable. However, diagnostic performance of a binary system (positive vs. negative) was more specific than margin distance classification (positive or <1 vs. ≥1 mm from tumor), but less sensitive in predicting local recurrence. The American Joint Committee on Cancer R classification (R0 vs. R1/R2) seems to adequately stratify patients by risk for local recurrence after neoadjuvant therapy and subsequent surgical resection. Furthermore, close but negative resection margins (<1 mm from tumor) appear sufficient for local control of high-grade pleomorphic soft tissue sarcomas of the extremity or trunk in this clinical setting, with minimal reduction in the risk of local recurrence with increasing margin width or surgical clearance.