Abstract Disclosure: M.C. Oliveira: None. D. Paixão Côrtes Aguiar: None. E.R. Corso: None. C.G. Rech: None. J.F. Lima: None. Introduction: Prolactin can be a modulator of body composition and weight and has been associated with obesity. However, the data, especially regarding weight behavior when normalizing hyperprolactinemia, are controversial. Methods: We retrospectively reviewed our data on a large sample of patients with treated macroprolactinomas, with or without normalization of PRL levels. Results: The sample consisted of 73 patients, 35 F, 38 M, and 15 to 86 years. In 42 cases (57.5%), the MRI showed suprasellar extension of the tumor, and in 37 (50.6%) some sort of invasion. In the presentation, the patients' weight varied between 49 and 156 kg, and the BMI (n=69) was between 18 and 52. Obesity was present in 39 patients (56.5%) and overweight in 19 (27.5%). Obesity was classified as class 1 in 19 cases (48.7% of obese patients), class 2 in 7 (17.9%), and class 3 in 13 cases (33.3%). The occurrence of obesity showed no significant difference between gender (p= 0,627) or the presence of suprasellar tumor extension. Of the patients with invasion (38/68), 92% were obese or overweight, with a significant association between both (p= 0,05). The obesity/overweight did not show an association (p= 0.716) with hypopituitarism or with specific deficiencies: GH, ACTH, and TSH, all with p= 1,000, and hypogonadism, p= 0,649. There was no correlation between initial weight and PRL levels (r= -0.033; p= 0.783). The follow-up ranged from 6 and 202 months. All patients used, at some point, bromocriptine or cabergoline. In 51 cases (69.9%) the PRL normalized. Of those who did not normalize, 19 had a reduction in the PRL level superior to 50%, in 14 cases in a percentage greater than 90%. There was a correlation between the initial weight and the percentage reduction in PRL at the last visit: higher initial weights correlated with smaller reductions in PRL (r= -0.470; p= 0.042). The last weight (n 64) was 89 ± 23,8 kg and the last BMI was 31,4 ± 6,9. In 36 cases (56.3%) the weight decreased: 18 of them with significant loss (reduction >5% of initial weight). Another 27 patients (42.2%) had weight gain: 18 of them with significant gain (>5% of the initial). In 12 patients, there was a class change in weight rating, 5 cases for a better classification and 7 for a worse. Significant weight loss was not associated with PRL normalization, p= 0.149. Conclusion: The prevalence of obesity and overweight in patients with macroprolactinomas far exceeds that found in the general population. In one-third of the cases, obesity is class 3. A meaningful association between obesity and tumor invasion was observed. There was no correlation between initial weight and PRL levels, and significant weight loss was also not associated with PRL normalization. Presentation: Friday, June 16, 2023