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Objectives Since the literature about giant (≥40 mm)pituitary somatotroph adenomas is limited to case reports, we aimed to summarize the characteristics of our giant somatotroph pituitary adenoma cohort and compare their clinical features and treatment responses with somatotroph macroadenomas. Materials and Methods This retrospective study included 16 patients (6 F/10 M) and 57 patients (29 F/28 M) with adenoma sizes ≥40 mm and 20-39 mm, respectively. The patients with <40 mm adenoma size were further divided into subgroups with adenoma size 20-29 mm (26 patients) and 30-39 mm (31 patients). Preoperative and postoperative hormone profiles, imaging and pathological findings, number of surgeries, presence of residual tumor, treatment modalities (including somatostatin receptor ligands, dopamine receptor agonists, pegvisomant, radiotherapy) and remission status were compared between groups. Results In giant somatotroph adenomas group, mean value of the preoperative maximal diameter of adenoma was 44.8±10.1 mm (range 40-80 mm). Mean age at diagnosis was 31.8±12.6 years (range 11-55). Mean preoperative GH level was 127.4±257.1 ng/mL. The highest GH level was measured as 951 ng/mL in a female patient having a giant pituitary adenoma with a maximum diameter of 50 mm. Mean baseline IGF-1 level was 2.33±1. 04×ULN (upper limit of normal) for age and sex. Mean number of surgery was 2.4±1.5 (range 1-6) and mean number of treatment modalities applied to achieve hormonal remission postoperatively was 2.1±0.9 (range 1-3). After a mean duration of follow-up of 11.2±6.5 years (range 1-21 years), hormonal remission and partial control were achieved in nine and two patients, respectively. In the group with adenoma size <40 mm, mean value of the preoperative maximal diameter of adenoma was 28.4±5.2 mm (range 20-38 mm) and mean age at diagnosis was 35.8±10.5 years (range 15-62). When we compare the groups, the number of surgeries was significantly higher in giant adenoma group in which 11 of 16 patients (68.8%) underwent repeated surgeries (p=0. 009). The rate of gross total resection tended to decrease as tumor size increases. While radiotherapy was given to 62.5% of the patients with giant adenoma, it was applied to 26.9% and 35.5% of the patients in the groups with adenoma size 20-29 mm and 30-39 mm, respectively (p=0. 068). The total number of treatment modalities applied to achieve hormonal remission postoperatively tended to be higher with increasing adenoma size, although not statistically significant (p=0. 062). Although preoperative GH and IGF-1 levels and Ki-67 index tended to be higher with increasing adenoma size, there was no statistically significant difference between the groups in terms of these variables. Hormonal remission rates were similar between groups. Conclusion Giant somatotroph adenomas require an aggressive multimodal treatment approach and advanced care to achieve sustainable hormonal remission. Presentation: No date and time listed