Acromegaly is a rare, chronic disorder that mostly results from growth hormone (GH)-secreting pituitary adenoma. Transsphenoidal surgery is the first-line treatment of this adenoma. This study aimed to identify factors associated with remission outcome in patients with GH-secreting pituitary adenomas following transsphenoidal surgery. Patients with GH-secreting pituitary adenomas who underwent transsphenoidal surgery for tumor removal at Songklanagarind Hospital between January 2003 and December 2019 were retrospectively reviewed. The primary outcome was the remission of disease at the last follow-up using 2000 and 2010 consensus criteria. Using logistic regression analysis, various factors were analyzed for association with disease remission outcome. This study included 51 patients. The remission rate of GH-secreting pituitary microadenomas and macroadenomas following transsphenoidal surgery were 100% and 43.75%, respectively. Multivariate analysis showed that preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were significantly associated with nonremission outcome (P < 0.001 and P = 0.012, respectively). Patients with both of these factors had poor outcomes and never achieved remission after treatment, while patients with neither of these factors had high remission rates (87.5%) following surgery. Four of 6 (66.7%) patients who underwent repeat surgery gained remission. Preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were important prognostic factors that determined remission outcome after treatment. Patients who have both of these poor prognostic factors should be aggressively treated with surgery, medication, and probably radiation to optimally control the disease.