Therapeutic effects of presurgical long-acting octreotide treatment on tumor shrinkage, and short- and long-term postoperative GH and IGF-1 levels of acromegaly patients with invasive pituitary macroadenomas were investigated prospectively in Huashan Hospital, Shanghai, China. Thirty-nine untreated acromegaly patients, all with invasive pituitary macroadenomas, were randomly divided into two groups: experimental group (n=19), and control group (n=20). Patients in the experimental group received a three-month course of long-acting octreotide treatment before transsphenoidal surgery; the control group underwent surgery directly. Tumor shrinkage after drug treatment and short- and long-term postoperative GH and IGF-1 levels were analyzed in the two groups. Long-acting octreotide treatment reduced tumor size from 7893 ± 6450 to 4794 ± 4682 mm(3). Mean shrinkage rate was 37.4 ± 30.9%. GH and IGF-1 levels of the experimental group were lower than the control group at 3 months, 6 months after surgery, and after long-term follow-up. Remission rate (both GH and IGF-1 normal) of the experimental group was higher at 3 and 6 months follow-up, but exhibited no advantage in long-term follow-up. In the experimental group, the total resection rate was higher in patients whose Hardy-Knosp grading decreased to ≤ 2 than those whose Hardy-Knosp grading is still ≥ 3 after drug pretreatment. In conclusion, presurgical long-acting octreotide treatment effectively reduces tumor size and invasion, which helps enhance early remission rates of invasive macroadenomas by transsphenoidal surgery, but does not appear to improve the long-term cure rate.