Background - We examined treatment-seeking overweight and obese youths to better understand the gender, age, and treatment modality differences in generic and disease-specific health-related quality of life (HRQOL). Methods - This multicenter study included 1,916 patients (mean = 12.6 years; 57% females; mean zBMI = 2.4) who started treatment for overweight and obesity in 48 treatment facilities between July 2005 and October 2006. The facilities offered either inpatient treatment or outpatient programs. Prior to treatment, all participants completed the generic KIDSCREEN-27 HRQOL-questionnaire, the self-perception subscale of the generic KIDSCREEN-52 and the disease-specific obesity module of the KINDLR. The patients' HRQOL was compared to the KIDSCREEN reference sample from the general population by one-way analyses of variance, adjusting for age, gender, and socioeconomic status. Independent t-tests were conducted to compare disease-specific HRQOL scores between patients by gender and age group. Significant mean differences in HRQOL between inpatients and outpatients were explored by one-way analyses of variance, adjusting for age, gender, and zBMI. Effect sizes 'd' were calculated employing the estimated marginal means and the pooled standard deviation (mtreatment - mnorm/SDpooled). Results - The patients' HRQOL scores were impaired relative to German norms, with effect sizes up to d = 1.12. The pattern of impairment was similar in boys and girls as well as in children and adolescents. In each of the analyses, at least three of six KIDSCREEN subscales were affected. Regardless of gender and age group, the highest impairments were found in self-perception and physical well-being. Because of the strong decrease in HRQOL in the general population during adolescence, compared to age-specific norms, adolescents were less impaired than were children. However, overweight and obese adolescents (especially females) reported the lowest absolute HRQOL scores. HRQOL varied with the intensity of treatment. Inpatients had significantly lower scores than did outpatients, even after adjusting for age, gender and zBMI. Conclusions - The results suggest the presence of differences in HRQOL with regard to gender, age, and treatment modality in treatment-seeking overweight and obese youths. Research and clinical practice must consider the particular impairments of inpatients as well as the impairments of (especially female) adolescents.