Object. Microscopic Rathke cleft cysts are a common incidental autopsy finding, but some Rathke cleft cysts can become sufficiently large to cause visual impairment, hypothalamic-pituitary dysfunction, and headaches. In this study patients were evaluated pre- and postoperatively to ascertain the clinical significance of surgical intervention on endocrine and visual improvement. Factors correlated with cyst recurrence were also evaluated. Methods. A retrospective analysis was conducted in 160 patients with Rathke cleft cysts who were treated between 1984 and 1995 and completed at least a 5-year follow-up period. Of these 160 patients, 118 initially exhibited symptoms of visual impairment or endocrine dysfunction, became symptomatic during the follow-up period, or were found to have cyst enlargement. These 118 patients underwent transsphenoidal surgery. Forty-two patients with incidental lesions that demonstrated no growth on magnetic resonance (MR) images were followed up without an operation. Complete resection, as observed on MR images 3 months postoperatively, was obtained in 114 (97%) of 118 patients. Vision improved postoperatively in 57 (98%) of 58 patients. Hypogonadism improved in 11 (18%) of 62 patients, growth hormone deficiency resolved in 14 (18%) of 78 patients, and hypocortisolemia resolved in one (14%) of seven patients. Twenty-two patients (19%) began to exhibit symptoms of diabetes insipidus, which had not been present preoperatively. The total 5-year recurrence rate was 18% (21 of 118 patients), with 12 patients requiring a repeated operation. Surgical and pathological factors that were found to be statistically associated with recurrence were the use of a fat and/or fascial graft for closure (p < 0.01) and the presence of squamous metaplasia in the cyst wall (p < 0.01). The extent of resection of the cyst wall was not associated with an increased rate of recurrence. In 42 (69%) of 61 patients the incidental cysts did not progress on imaging studies or clinically. Conclusions. This is the largest series of patients with symptomatic Rathke cleft cysts who received operative intervention and participated in the longest postoperative follow up reported in the literature. The high recurrence rate (18%) supports the theory that a relationship exists between a symptomatic Rathke cleft cyst and craniopharyngioma. Improvements in visual and endocrine dysfunction can be expected after surgical decompression of the optic apparatus and the hypothalamic-pituitary axis.