Radical cystectomy represents the gold standard for locally advanced bladder cancer. Orthotopic neobladder is considered the surgical option which may offer the least modification of body image and the best life condition to the unfortunate patient requiring radical cystectomy. Objective of this study was to investigate long term clinical outcome of orthotopic ileal bladder substitute with special reference to late complications and patient compliance. Twenty male patients 48 to 71 years old (mean age 59.8 + 7.4 years) underwent radical cystectomy and Studer orthotopic ileal neobladder for invasive carcinoma of the bladder. Before surgery all patients filled in a phycometric test for evaluating their knowledge capacity; after surgery they underwent a course of biofeedback and instructed to avoid overfilling of the neobladder with timed micturitions and a regular regimen of fluid intake. Pressure flow study was included in the routine follow-up carried out at six months and then yearly. Seventeen patients (85%), with a good knowledge capacity, reported a good compliance to the modified life style imposed by the bladder substitute, they all were dry during the day with 3 to 5.5 hour interval between micturitions; fourteen of these patients were continent at night with timed micturitions every 3-4 hours (mean: 3.2); an average cystometric capacity of 450 ml was found in these patients with no residual urine; three patients (18%) had incontinence episodes once or twice a week during the night; no decompensation of the neobladder, significant ureteral reflux or dilatation were reported; elongation of the afferent loop was found in one patient following small bowel resection for ileal volvulus. Three patients (15%), with a reduced knowledge capacity, who did not follow the suggested life style: fluid intake was irregular, micturitions were not timed during both day and night time, had residual urine larger than 400 ml. and incontinence episodes requiring pads; nevertheless no dilation of the upper urinary tract was found. Our experience suggests that careful compliance of patients to the new life style imposed by the orthotopic neobladder is of importance to avoid its decompensation. The possible causative role of gastrointestinal hormones such as enteroglucagon (EG) and peptide tyrosine-tyrosine (PYY) in the elongation of the afferent limb of the Studer neobladder is proposed. In conclusion, we believe that orthotopic ileal neobladder is an ideal surgical option on in the young, educated and cooperative patients.