Background Lipedema is a loose connective tissue disease predominantly in women identified by increased nodular and fibrotic adipose tissue on the buttocks, hips and limbs that develops at times of hormone, weight and shape change including puberty, pregnancy, and menopause. Lipedema tissue may be very painful and can severely impair mobility. Non-lipedema obesity, lymphedema, venous disease, and hypermobile joints are comorbidities. Lipedema tissue is difficult to reduce by diet, exercise, or bariatric surgery. Methods This paper is a consensus guideline on lipedema written by a US committee following the Delphi Method. Consensus statements are rated for strength using the GRADE system. Results Eighty-five consensus statements outline lipedema pathophysiology, and medical, surgical, vascular, and other therapeutic recommendations. Future research topics are suggested. Conclusion These guidelines improve the understanding of the loose connective tissue disease, lipedema, to advance our understanding towards early diagnosis, treatments, and ultimately a cure for affected individuals.