Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.