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Object: The question of whether preoperative therapy with somatostatin analogs can improve surgical outcome in acromegaly has not been definitively answered. In this paper, the authors report the effects of preoperative treatment with somatostatin analogs in a large sample of patients with acromegaly., Methods: Between 1990 and 2003, 399 consecutive patients with acromegaly underwent surgery at the Istituto Scientifico San Raffaele. Thirty-three patients who had previously undergone surgery or radiation treatment, 48 patients treated with somatostatin analogs for fewer than 3 months, and patients who had stopped therapy for too long a time before surgery were excluded from the study. One hundred forty-three patients who had received somatostatin analogs prior to surgery (Group 1) were randomly matched to 143 patients who had never been treated with somatostatin analogs (Group 2). Matching criteria were tumor size and invasiveness into the cavernous sinus. Before surgery, Group 1 patients showed reduction of growth hormone levels to less than 50% of baseline in 64% of cases, but insulin-like growth factor-I was normalized in only 19.5%. Surgical remission occurred in 81 Group 1 patients (56.6%) and in 91 Group 2 patients (63.6%; p = 0.28). No significant difference in the remission rate was observed when cases were analyzed according to tumor size or invasiveness. Logistic regression analysis confirmed that pretreatment with somatostatin analogs was not associated with surgical outcome. Surgical morbidity was mild and similar in Group 1 and Group 2 patients (7 and 5.6%, respectively; p = 0.81). Surgical remission and complication rates in patients with acromegaly who received treatment with somatostatin analogs prior to surgery were not significantly different from those of matched patients who did not receive these agents., Conclusions: At present, the routine use of presurgical therapy with somatostatin analogs for patients with acromegaly cannot be recommended.