Combination surgery and radiotherapy (RT) is frequently used in soft tissue sarcoma (STS). Because lower doses and smaller irradiation volumes are possible in preoperative RT (pre-op RT), this approach can be especially valuable in anatomic settings where critical organs are in close proximity to the RT target area. A recent multicenter phase III trial (SR.2 trial of the National Cancer Institute of Canada Clinical Trials Group) comparing pre-op RT against post-op RT for extremity STS has shown significantly higher major wound complication rates (35%) with pre-op RT. We postulated that wound complication rates may be less frequent in the head and neck with better vascularity and wider use of secondary wound reconstruction. Using a prospective database, we identified 40 consecutive patients with head and neck STS treated with pre-op RT (50 Gy) and subsequent (4 to 6 weeks later) resection between 1/89 and 8/99 in a single institution setting. Major wound complications (MWC) were classified by the identical criteria used in the SR.2 trial. Intracranial extension was evident in 5 patients, whereas 50% of the patients had large tumors (> 5 cm). Deep tumor was present in 34 (85%), and 6 (15%) were superficial to fascia. In this series, 31 patients (77.5%) had secondary reconstruction of the acquired soft tissue deficit. The actuarial 2-year local relapse-free rate was 80%, and the metastatic relapse-free rate was 85%. Major wound complications occurred in 8 of 40 patients (20%) within 120 days of surgery according to the SR.2 criteria: secondary wound surgery (3), readmission or prolonged hospital admission for wound care (2), deep packing (0), prolonged dressing changes (2), and invasive procedure for wound care (1). The latter was a minor wound management problem (a single outpatient drainage of a seroma) for the combined rate of 8/20 or 20%. Our findings show that (1) pre-op RT in head and neck STS is associated with lower rates of major wound complications compared to extremity cases; (2) pre-op RT provides high rates of local control in an adverse group of cases of adult head and neck STS; (3) the choice of scheduling of RT should be based on anatomic issues with emphasis on the trade-offs between RT doses and volumes versus wound morbidity for individual patients. This is especially important when tumor may be adjacent to critical head and neck structures which may be protected from the high-dose RT area.