OBJECTIVE To describe an association of growth hormone (GH) secreting pituitary microadenomas and empty sella (ES), which has been described in case reports - the underlying mechanisms are unclear. METHODS We retrospectively analyzed patients operated for GH-producing pituitary adenomas between February 2004 and February 2009. Magnetic resonance imaging (MRI), computed tomography (CT) imaging, and pituitary function testing were performed. All cases underwent transsphenoidal surgery (TSS). Mean follow up was 38 months (range 12-80 months). RESULTS Out of 152 patients with acromegaly due to GH-producing pituitary adenomas (female:male=73:79; age range 17-63 years), 69 patients had microadenomas (45.4%; 38 females, 31 males). We found 14 cases (14/69, 20.3%), all microadenomas, with presurgical evidence of ES - 10 females (71%) and 4 males (29%) (female:male=2.5:1). When compared with 103 patients with GH-negative microadenomas treated in the same time period (ES in 4 of 103; 3.9%), ES was highly significantly associated with GH production by the microadenoma (p=0.001). In acromegalics with empty sella, no cases of ectopic adenoma were found. Postoperatively, GH and IGF-1 levels fell in all patients, and 7 cases had random GH and IGF-1 levels consistent with cure. CONCLUSION The combination of GH-producing microadenomas and empty, enlarged sella is not rare. In this setting, preoperative CT scans are very useful and the transsphenoidal approach is efficient and safe. The mechanism underlying the association of GH-producing microadenomas and empty sella remains unclear and requires further studies.