Context: Transsphenoidal surgery (TSS) is the primary treatment of choice in acromegaly. It is important to identify patients in whom surgical cure is not attainable at an early stage, both to inform patients on expected treatment outcome and to select those who are more likely to need additional therapy. Objective: To identify predictors for remission after TSS in acromegaly. Methods: Large multicenter study with retrospective data collection from 3 tertiary neurosurgical referral centers in The Netherlands. We analyzed clinical data since 2000 from 3 cohorts (Groningen, Nijmegen, and Rotterdam, total n=282). Multivariate regression models were used to identify predictors of early biochemical remission (12 weeks to 1 year postoperatively) according to the 2010 consensus criteria, long-term remission (age-and sex-normalized insulin-like growth factor 1 [IGF-1] and the absence of postoperative treatment until last follow-up), and relative IGF-1 and growth hormone [GH] reduction. Results: A larger maximum tumor diameter (odds ratio [OR] 0.91, 95% CI 0.87-0.96, P≤.0001) was associated with a lower chance of early biochemical remission. A larger maximum tumor diameter (OR 0.93, 95% CI 0.89-0.97, P=.0022) and a higher random GH concentration at diagnosis (OR 0.98, 95% CI 0.96-0.99, P=.0053) were associated with a lower chance of long-term remission. Conclusion: Maximum tumor diameter and random GH concentration at diagnosis are the best predictors for remission after TSS in acromegaly.