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Long-acting somatostatin analogs are frequently used as adjuvant treatment of acromegaly patients after noncurative surgery. This sudy aims to compare the efficacy of octreotide long-acting release (OCT) and lanreotide Autogel (LAN) in acromegaly patients. Sixty-eight patients not cured by transsphenoidal endoscopic or microscopic pituitary surgery between 2003 and 2009 were retrospectively analyzed (25 men; 43 women; mean age 41.1 ± 10.9 years [range 18-65 years]). The patients were assigned randomly to OCT (n = 36) and LAN (n = 32) groups. Evaluations included insulin-like growth factor I (IGF-I) and growth hormone (GH) after oral glucose tolerance test (OGTT) 3, 6, 12 and 18 months after starting medical treatment; pituitary magnetic resonance imaging was performed before treatment and after 3 and 12 months. Patients achieving IGF-I levels within the age and gender normal range and GH level <1 μg/l following OGTT were considered a 'biochemical cure'. Mean IGF-I and GH values and tumor volumes (cm(3)) in the LAN and OCT groups were similar in the post-operative period before initiation of medical treatment. A statistically significant decrease in GH and IGF-I levels was obtained for both treatment groups at each follow-up visit compared to the previous value. Tumor shrinkage after 12 months of treatment was statistically significant in both groups but the percentage tumor shrinkage (28.5% vs. 34.9%, P = 0.166) and rate of patients achieving biochemical cure (63.9 and 78.1%, P = 0.454) were similar between OCT and LAN groups, respectively. OCT and LAN treatment options have similar efficacy for ensuring biochemical cure and tumor shrinkage in acromegaly patients who had noncurative surgery.