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Prolonged activation of pain centers is a proposed cause of chronic pain syndromes. Women are at particular risk for chronic pain as they tend to more readily detect pain and to attenuate it less than men. We set out to determine whether sex affected pain and recovery after major surgery by analyzing data originally collected to determine the effect of the timing of epidural analgesia on long-term outcome after thoracotomy.Patients presenting for lobectomy, segmentectomy, or bilobectomy, but not pneumonectomy or chest wall resection, were enrolled. Pain, physical activity, and the extent that pain interfered with activities after surgery were prospectively assessed with standard questionnaires (Brief Pain Inventory and physical component score of SF-36) on postoperative days 1 to 5, and at postoperative weeks 4, 8, 12, 24, 36, and 48 by a blinded research assistant. Perioperative care was standardized and included patient-controlled thoracic epidural analgesia until thoracostomy tube removal.Fifty eight men and 62 women were enrolled. Women reported more pain than men throughout the entire study period, and they had a higher rate of nonsteroidal anti-inflammatory drug use, but not opioid use. This increased pain was not explained by incision type, surgeon, tumor type, or tumor stage. Older patients reported less pain after discharge than younger patients. Postoperative physical activity levels were significantly less than those reported preoperatively, but did not differ by sex.Women have a distinctly different pain experience than men after thoracic surgery and probably require novel and/or multimodal analgesic regimens to improve their comfort.