Intrauterine progestin is a treatment option for women with atypical hyperplasia or low-risk endometrial cancer who wish to preserve their fertility, or whose poor surgical fitness precludes safe hysterectomy. We hypothesized that in such women with obesity, weight loss during progestin treatment may improve oncological outcomes. We conducted a prospective non-randomized study of women with obesity and atypical hyperplasia or low-grade stage 1a endometrial cancer undergoing progestin treatment. Women with a BMI≥35kg/m2 were offered bariatric surgery; those who declined and those with BMI 30-34.9kg/m2 were encouraged to lose weight by low-calorie diet. We assessed uptake of bariatric surgery; weight lost during progestin treatment; and the impact of >10% total body weight loss on progestin treatment response at 12 months. 71 women [median age 58years (IQR 35-65); mean BMI 48kg/m2 (SD 9.3)] completed the study. 23 women (32%) had bariatric surgery, on average 5 months (IQR 3-8) after progestin treatment commenced. Weight change during progestin treatment was -33.4kg (95%CI -42.1, -24.7) and -4.6kg (95%CI -7.8, -1.4) in women receiving bariatric surgery and low-calorie diet, respectively (p<0.001). 43 women (61%) responded to progestin, while 23 (32%) showed stabilized and 5 (7%) progressive disease. Response at 12 months was not predicted by age or baseline BMI, but women who lost >10% of their total body weight were more likely to respond to progestin than those who did not (adjusted odds ratio 3.95; 95%CI 1.3, 12.5; p=0.02). Thus weight loss may improve oncological outcomes in women with obesity-associated endometrial neoplastic abnormalities treated with progestin.