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To examine the effect overactive bladder (OAB) and other lower urinary tract symptoms (LUTS) on health-related quality of life (HRQoL) in a population sample, as OAB often occurs in conjunction with many other LUTS.A nested case-control analysis was performed on men and women with (cases) and without (controls) OAB, from the EPIC study. OAB was assessed using 2002 International Continence Society definitions. Based on their responses to questions about LUTS, cases were classified into five groups; continent OAB, OAB with incontinence, OAB + postmicturition, OAB + voiding, and OAB + postmicturition + voiding. Both cases and controls were asked questions about symptom bother (OAB-q), generic QoL (EQ-5D), work productivity (Work Productivity and Activity Impairment, WPAI), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sexual satisfaction, and erectile dysfunction (men only) using the Massachusetts Male Aging Study. Cases answered additional condition-specific questions HRQoL (OAB-q short form), Patient Perception of Bladder Condition and work productivity related to a specific health problem (WPAI-SHP). General linear models were used to evaluate group differences.Of the EPIC participants, 1434 identified OAB cases were matched by age, gender and country, with 1434 participants designated as controls. Cases and controls were primarily Caucasian (96.2% and 96.7%, respectively), and most (65%) were female; the mean age was 53.8 and 53.7 years, respectively. Comorbid conditions differed significantly by case/control status, with cases reporting significantly greater rates of chronic constipation, asthma, diabetes, high blood pressure, bladder or prostate cancer, neurological conditions and depression. There were significant differences between the cases and controls in all reported LUTS. The OAB + postmicturition + voiding group reported significantly greater symptom bother, worse HRQoL, higher rates of depression and decreased enjoyment of sexual activity, than the other subgroups.OAB has a substantial, multidimensional impact on patients; OAB with additional LUTS has a greater impact. The diagnosis and treatment of OAB should be considered in conjunction with other LUTS, to maximize treatment options and optimize patient outcomes.