Objective: The aim of this study is to evaluate clinical data from a large cohort of acromegalic patients with and without hyperprolactinemia. Design and methods: Between January 2002 and June 2010, a set of data on 279 acromegalic patients undergoing transsphenoidal surgery was available. Based on preoperative GH and prolactin (PRL) levels, patients were divided into GH and GHCPRL groups. A stabilization or a further improvement of postoperative changes in clinical, hormonal, immunohistochemical, and magnetic resonance imaging parameters was observed in all patients throughout the follow-up period. Results: The GH group had significantly more coarse facial features, large hands and feet, hypertension, and diabetes mellitus compared with the GHCPRL group but significantly less menstrual disorders (13.8 vs 54.3%, P!0.001) and galactorrhea (3.1 vs 22.4%, P!0.001). The GH group had a higher age at diagnosis compared with the GHCPRL group (45.6G13.9 vs 40.4G11.4 years, PZ0.001). The GH group had a smaller mean maximal diameter of the adenomas (2.2G0.9 vs 2.6G1.1 cm, PZ0.004). There were no significant correlations between hormone levels and the immunohistochemical results. According to the criteria for hormonal cure of acromegaly, the surgical control rates in the GH and GHCPRL groups were 68.4 and 59.7% respectively (PZ0.187). Tumor size was an important factor that affected the results of the operations. The rates of surgical control in GH and GHCPRL groups were 80.7 and 69.1% respectively (PZ0.037), and the recurrence rates in the two groups were 7.1 and 11.3% respectively (PZ0.185). Conclusions: Compared with patients with merely GH-secreting adenomas, acromegalic patients with hyperprolactinemia are characterized by an earlier onset of disease, lesser acromegalic features, lower GH levels, but larger tumor sizes, whereas in female patients, GH-PRL secreting adenomas are associated with higher incidences of menstrual disorders and galactorrhea.