The influence of primary systemic therapy in treating operable breast cancer on postmastectomy morbidity rates was investigated. The contribution of other risk factors was assessed by multiple logistic regression. Seventy-nine eligible patients were randomly allocated, 39 to undergo immediate modified radical mastectomy, and 40 to receive initial cytotoxic or endocrine treatment followed by mastectomy. Postoperative wound seroma, infection and necrosis were recorded prospectively. Fourteen minor and six major complications occurred in 17 patients treated conventionally, while 14 patients developed 11 minor and six major complications after systemic therapy (P > 0.4). Median hospital stay was 8 days for both groups. Age, smoking, immediate breast reconstruction and the type of primary systemic treatment given were not independent predictors of complication risk. Obesity emerged as a significant risk factor for postmastectomy complications (P = 0.015). Primary systemic therapy does not increase the rate of morbidity after mastectomy.