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Background Acromegaly is a rare disorder resulting from benign growth hormone (GH)-secreting pituitary adenomas in 90% of the cases. In recent years, many researchers have studied the Ki-67 index level of pituitary tumors and its relationship with demographics, biochemical parameters, clinical behavior, and recurrence rate. Objectives This study aimed to evaluate the correlation of Ki-67 index level with clinicoradiological and endocrinological parameters in confirmed GH-secreting pituitary adenomas, as well as with the surgical response and medical treatment after surgery. Methods We collected the medical and pathologic records of 49 patients with GH-secreting pituitary adenoma who underwent surgeries from 2008 to 2017 in Shariati hospital affiliated to Tehran University of Medical Sciences. Results According to MRI reports, 94% of the tumors were macroadenomas. The MRI findings also revealed the median maximal adenoma diameter of 18.5 mm. About 40% of the patients achieved remission three months after the surgery. Younger patients had a significantly higher Ki-67 index level (P = 0.036). We did not observe any significant difference in the Ki-67 index level regarding gender, tumor type, maximal tumor diameter, tumor invasiveness, tumor secretory type, and remission. Interestingly, the Ki-67 index level was negatively correlated with the insulin-like growth factor-1 (IGF-1) level at the last follow-up (P = 0.02). In logistic regression analysis, patients with higher preoperative GH serum levels had a better outcome. Conclusions Our results indicated a negative correlation between age and Ki-67 index level. However, there was no association between the Ki-67 index level and some tumor behaviors, as well as short- and long-term remission.