Study Question: Which of the competing models of the Endometriosis Health Profile 30 Questionnaire (EHP-30) factor structure is best supported by confirmatory factor analysis (CFA)?, Summary Answer: Findings support a five-factor first-order model of the EHP-30, thereby lending support to the model originally suggested by the questionnaire developers., What Is Known Already: Endometriosis has a negative impact on quality of life, and measures specifically developed to address this impact, such as the EHP-30, are vital in research and disease management. Previous studies have found different models of the EHP-30 factor structure, and generated uncertainty regarding how to use the questionnaire. CFA can be applied to compare competing factor models and determine the underlying structure of a questionnaire., Study Design Size Duration: This cross-sectional multicenter study included 304 women with endometriosis recruited from three different public health service endometriosis clinics (referral centers for treatment of severe endometriosis) and the Danish Endometriosis Patients Association from 2014 to 2015., Participants/materials Setting Methods: Diagnosis of endometriosis was confirmed in medical records for 84.2% and by histology for 66.8% of participants. Questionnaires (the licensed Danish version of the EHP-30) were sent by post two times with a 6- to 12-week interval. CFA was used to examine construct validity and Bland-Altman plots to examine test-retest reliability and the convergent validity with the Short Form 36 version 2., Main Results and the Role of Chance: Response rate was high (87.6%). CFA supported the original first-order five-factor structure of the EHP-30, and thereby, the use of five separate scale-scores in clinical and research practice. Visual inspection of Bland-Altman plots suggested excellent test-retest reliability of the EHP-30 and supported the use of a disease specific quality of life instrument for women with endometriosis., Limitations Reasons for Caution: Diagnosis could not be confirmed through histology data in 33.2% of participants. However, subgroup analyses based on women with confirmed histology only, yielded similar results. Data related to menstrual cycle stage and the use of hormonal and pain medication during questionnaire completion were not collected. A larger study, including data from different countries on different continents, would be better designed to exclude potential population bias., Wider Implications of the Findings: EHP-30, with its original five-factor structure, appears to be a valid, stable, and specific quality of life measure for women with endometriosis. It seems easy to understand, quick to administer, and importantly, scoring might be unaffected by cyclical/menstrual pain symptoms related to endometriosis. The finding of a five-factor model from different studies across several countries supports the crosscultural validity of the EHP-30., Study Funding/competing Interests: This work was supported by the Danish Endometriosis Association, which is a nongovernmental organization run by women with endometriosis and by a scholarship from the Health Research Fund of Central Denmark Region. The authors have no conflicts of interest., Trial Registration Number: The Danish Data Protection Agency (J.nr: 2013-41-2264)., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)