Quality of life assessment has emerged as an important approach to evaluate the effect of pancreas transplantation in diabetic patients with end-stage renal failure (ESRD). The aim of this study was to evaluate the impact of the ESRD treatment modality on the quality of life in patients with Type I (insulin-dependent) diabetes mellitus. Thirty-two patients of similar age, sex and diabetes duration, treated for more than 1 year with simultaneous kidney and pancreas transplantation (Group 1, n = 12), or kidney transplantation (Group 2, n = 10), or hemodialysis (Group 3, n = 10) were studied. Quality of life was assessed using a questionnaire (34 questions with 103 possible answers) including social (sickness pension, working capacity) and subjective (general health perception), index of Spizer and index of reintegration to normal life of Wood Dauphine) quality of life indicators, working capacity, as well as physical ability (Karnofsky index), sports training and sexual activity. Patients in Group 1 showed highest scores on general health perception (p = 0.012), Karnofsky index (p = 0.076) and sexual activity (p = 0.026). There were no significant differences between groups on social index, as well as index of Spizer, index of reintegration to normal life and sport activity. Patients on hemodialysis treatment presented the lowest scores in all the items evaluated. In conclusion, in our experience simultaneous pancreas and kidney transplantation is the treatment modality that offers better quality of life to diabetic patients with ESRD; however, this does not translate into a higher socio-labor yield.