OBJECTIVE: Compare the Health Related Quality of Life (HRQoL) and Psychological Well-being (PW) of IBS and non-IBS patients (controls) and evaluate the perceived stress of IBS patients' relatives. METHODS: Observational, prospective study including a sample of 455 IBS patients meeting Rome II criteria, 69 controls, and 195 IBS patients' relatives. The controls were selected from those subjects who had attended a health centre with a relative due to digestive problems (excluding IBS). All samples were selected from the consulting rooms of 86 Spanish gastroenterologists and physicians. In order to measure HRQoL and PW patients and controls completed the EQ-5D and Psycological Well-Being Index (PGWBI). Patients' relatives completed an adapted version of the Levenstein's Perceived Stress Questionnaire' (LPSQ). RESULTS: The mean (SD) age of patients was 43(14) years and 76.5% were female. There were no statistical significant differences in age and gender between patients and controls. 67.9% of patients presented some concomitant disease, while in controls the percentage was lower (39.1%) (p<0,01). Patients presented worse HRQoL than controls, presenting a higher presence of problems in all EQ-5D dimensions (p<0,05), except self-care. 76.5 and 54.7% of patients declared having pain and anxiety problems, respectively, compared to 15.9 and 20.3% of controls. In terms of PGWBI, patients presented more problems than controls in all dimensions (p<0,05) except 'alimentation' and 'sexual relations'. Relatives obtained a mean (SD) LPSQ score of 0.54 (0.12) on a scale from 0 to 1 (maximum stress). Relatives of patients with a higher IBS severity (rated by patients and doctors) showed a higher stress level than those relatives of less severe patients. CONCLUSIONS: Patients with IBS showed a significant deterioration in HRQoL, in almost all HRQoL dimensions, compared with non-IBS subjects. Relatives showed varying levels of stress according to the patient's IBS severity, stress being higher in relatives of more severe patients.