Context: Transsphenoidal surgery is considered first-line therapy for acromegaly; however, there is often a need for adjunctive therapy. Somatostatin analogs (SSA) have greatly improved the effectiveness of medical treatment, but one third of patients are resistant. Objective: The aim was to evaluate whether magnetic resonance imaging (MRI) signal could predict long-term response to SSA in patients with active acromegaly after neurosurgery. Patients and Methods: Sixty-two patients whowere active acromegalic after surgery were included in this retrospective study. Remaining pituitary tumor was classified as hyper-, iso-, or hypointense by evaluating T2-weighted MRI signal. Treatment with SSA at maximal effective doses was prescribed and evaluated at 6 and 12 months by monitoring IGF-I, GH, and T2 MRI. Results: Complete response to SSA treatment (defined as normal IGF-I) at 6 months was observed in 30%, partial response (defined as IGF-I between 2 and 3 SD score) in 15%, and no response in55% of patients. At 12 months, 28, 20, and 52% were observed, respectively. MRI signal was hypointense in 40%, hyperintense in 48%, and isointense in 12%. At 6 months, complete response to SSA was observed in 71% of cases having hypointense MRI signal and in 20% of hyperintense (P = 0.04). At 12 months, 62% of hypointense remained well controlled, whereas in the hyperintense group, good, partial, or no response results did not change from that observed at 6 months (P = 0.04). Conclusion: In active acromegalic patients after surgery, a hypointense T2-weighted MRI signal is associated with a better response to SSA treatment at 6 and 12 months. Copyright © 2010 by The Endocrine Society.