Background: Mesenteric panniculitis (MP) is an uncommon benign inflammatory condition of unknown etiology that involves the adipose tissue of the mesentery. I can be evaluated as a single disease with two pathological subgroups: MP, representing the very large majoritary subgroup where inflammation and fat necrosis predominate and Retractile Mesenteritis, rarely found, where fibrosis and retraction predominate. Objective: To re-estimate the prevalence of MP in general population through a large prospective study, to compare the results with those of the literature and to evaluate the natural course of the condition. Methods: A continuous series of 613 consecutive unselected patients (280 females and 333 males) imaged with abdominal MDCT for various neoplastic (27%) or non neoplastic conditions (73%) constitutes the prospective material. A positive CT diagnosis of MP was based on the observation of at least three of five typical CT signs comprising: the presence of a well-defined “mass effect” on neighbouring structures (sign 1) constituted by mesenteric fat tissue of inhomogeneous higher attenuation than adjacent retroperitoneal or mesocolonic fat (sign 2), containing small soft tissue nodes (sign 3) typically surrounded by a hypoattenuated fatty “halo sign” (sign 4). Finally a hyperattenuating pseudocapsule may surround the all entity (sign 5). Results: A positive diagnosis of MP was made in 48 patients (prevalence of 7,83%) on the basis of the presence of at least 3 CT signs. After reconsidering the presence of the “halo sign” (sign 4) and of the “pseudocapsule” (sign 5) as “sine qua non” conditions for a positive diagnosis, a more restricted positive group of 21 cases was constituted (prevalence of 3,42%) comprising 10 males (3%) and 11 females (3,93%). There were 14 “non-neoplastic” patients – 6 males (2,27 %) and 8 females (3,6%) – and 7 “neoplastic” patients – 4 males (3,73%) and 3 females (5,17%) –. Conclusions: The prevalence of MP appears much higher than previously reported and the reason probably resides in the major technological evolution experienced in CT imaging during the last decade. This high prevalence probably explains the spontaneous association with the numerous and probably unrelated clinical situations found in the literature. Finally the vast majority of cases are considered as idiopathic, benign an asymptomatic. Except a discrete higher prevalence found in patients presenting with bladder and/or prostatic neoplasms and with lymphoma in group 1 the general prevalence of MP in our study doesn’t significantly differs in the “neoplastic” and “non neoplasic” groups of patients. We conclude that the value of MP in term of predictivity of an associated neoplasm is probably non relevant. Finally PET/CT is proved useful to correctly exclude mesenteric tumoral involvement in patients presenting with typical MP and follow-up studies show a great stability of the CT findings of MP in about 85% of cases.