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Giant pituitary adenomas (GPAs), defined as >/=40 mm in one extension, present a challenging subgroup of pituitary adenomas in terms of radical tumor removal and complication rates. The potential impact of intraoperative magnetic resonance imaging (iMRI) is investigated in a consecutive series and the results compared to the literature. From November 2004 until February 2005, six (five male) patients were operated for GPAs via an iMRI-guided transsphenoidal approach in the PoleStar N20. Clinical, endocrinological, and neuroradiological outcomes (at 3 months and yearly postoperative over 4 years) were assessed. Mean age was 46 years (range, 34-60). All patients presented with preoperative visual field defects, five with pituitary failure. Five adenomas were clinically nonfunctioning, one was producing GH and TSH. Preoperative imaging showed invasion of the cavernous sinus in all and extension to the interventricular foramen in two patients (one with occlusive hydrocephalus). Resection was total in four and subtotal (small cavernous sinus remnants) in two patients, leading to transsphenoidal reoperation in one patient. Visual acuity and fields improved in all six patients. The patient with occlusive hydrocephalus developed a postoperative cerebrospinal fluid leak (subsequently revised), two patients developed temporary, one permanent central diabetes insipidus, and one of them transient hyponatremia. Compared to the preoperative situation, endocrine status in the long-term follow-up (mean, 25 months) remained unchanged in four and worsened in two. Two patients were considered not to require hormone replacement therapy. IMRI supports transsphenoidal resections of GPAs because residual adenoma and related risk structures are easily detected and localized intraoperatively, extending the restricted visual access of the microscope beyond mere surface anatomy to a three-dimensional view. More radical removal of adenomas in a single surgical session combined with low complication rates are accomplished. This may add to a favorable clinical and endocrinological outcome in GPAs.