Abstract Disclosure: I. Ayalon-Dangur: None. E. Robenshtok: None. H. Duskin-Bitan: None. G. Tsvetov: None. A. Gorshtein: None. A. Akirov: None. I. Shimon: None. Objective: The treatment strategy for non-functioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medication, or follow-up. Data on non-operated patients with macroadenomas are sparse. This study sought to investigate the natural history of NFPAs followed without treatment. Design and patients: The database of a tertiary medical center was retrospectively searched (1995-2020) for adult patients with NFPA ≥10 mm who were naïve to surgery or medical treatment and were followed for ≥12 months after diagnosis. Patients with chiasmal threat were excluded. Follow-up was terminated if the patient underwent surgery, received cabergoline, or was lost to follow-up. Measurements: Data on tumor characteristics and size on imaging by MRI, symptoms including visual disturbances, and pituitary hormone levels were collected from the medical files. Tumor growth was defined as a maximal increase of >2 mm in diameter. Results: The cohort included 49 patients, 30 male and 19 female, of mean age 68.0±12.0 years. Median tumor size at diagnosis was 16 mm (range, 10-35), and median duration of follow-up was 3 years (range, 1-23(. Tumor’s size increased in 16 patients (33%), by a mean of 5.1±4.4 mm, and decreased in 10 patients (20%), by a mean of 3.5±1.3 mm; in 23 patients, the tumor remained stable. Overall, 33 patients (67%) were observed without intervention, 3 underwent surgery, and 13 received cabergoline. None of the parameters evaluated, including age, gender, baseline tumor size, tumor invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumor growth. Conclusions: Observation of NFPAs without surgery or medication is a reasonable approach in selected patients. In our study, there was no association of patient- or tumor-related parameters with tumor growth. Presentation: Thursday, June 15, 2023