This is a multicenter study on peroneal mononeuropathy (PM), in which a multidimensional protocol was performed to evaluate (1) the predisposing factors and their occurrence; (2) the relationships between the etiological, clinical, and neurophysiologic findings; and (3) disability and quality of life (QoL) in a wide sample with PM. Clinical and neurophysiologic evaluation was performed in all patients; moreover, the group adopted validated disability and QoL measurements to obtain more comprehensive and reliable data on PM. From November 2002 to January 2004, 69 patients were enrolled consecutively in 11 Italian centers. Our data showed that PM involves men more frequently than women (male : female = 4.1:1). PM was idiopathic (16%) or due to prolonged posture (23.1%), surgery (20.3%), weight loss (14.5%), trauma (11.6%), bedridden condition (7.3%), external compression from cast (5.8%), and arthrogenic cyst at the fibula (1.4%). Unexpectedly, peroneal nerve lesions were not only due to surgical operation close to the peroneal region but were also associated with thoracic-abdominal surgery. We observed conduction block in about 50-70% of postural and weight loss PM; in perioperative and idiopathic PM, conduction block or mixed damage was equally present; in PM due to trauma, we observed an exclusive axonal damage in about 60% of cases. Only in three cases (one postural PM, one idiopathic PM, and one weight loss PM), we observed a slowing of conduction velocity in the popliteal fossa-fibular head segment without conduction block. The comparison between QoL in patients with PM and in healthy subjects showed a significant involvement of physical and mental aspects. With regard to disability, 68% of patients walked with difficulty. Our data show that (1) most of the cases of PM are due to an identifiable predisposing factor; (2) there is a good correlation between predisposing factors and clinical-neurophysiologic findings; and (3) PM causes disability and deterioration of the physical and emotional aspects of QoL.