Craniopharyngioma (CP) is a mostly benign tumor that is nonetheless one of most formidable skull base lesions. CP tends to recur, and scarce clinical results are available regarding its long-term outcomes. From February 1996 to April 2002, craniopharyngiomas primarily resected by open surgery in a single-center and single-surgeon practice were screened. Medical information regarding patients' baseline, tumor parameters, endocrinological results, complications, and quality of life in those patients with a follow-up longer than 20years were reviewed. Nineteen out of 187 patients who met the inclusion criteria were eligible, and 78.9% of the patients were admitted due to visual deficits. The transcranial approach was mostly applied for the first attempt of opening resection, with 94.7% gross total resection. The size of the tumor ranged from 25 to 45mm with a mean maximal diameter of 34.7mm. Although 7 out of 19 patients received an extra procedure, 6 patients (31.5%) regained fertility, with 3 women bearing a total of 5 children and 3 men fathering a total of 4 children, during the 21.4-year follow-up (range: 20.0-23.3years). The mean Karnofsky Performance Status (KPS) score was 97.9 (range: 80-100) at the last follow-up, and the physical and mental 36-Item Short Form Health Survey (SF-36) scores were 88.0 and 80.5, respectively. The tumor sizes of the patients who regained fertility were not significantly different from those of the patients who remained infertile (t = 1.29, P > 0.2). The time interval from prior surgery to tumor resection for recurrent cases ranged from 0.3 to 17.4years (mean, 7.3years). There was no significant difference in the time until tumor recurrence in the patients who underwent a second surgery, a third surgery, or a fourth surgery. The satisfactory results in the present study revealed favorable long-term outcomes following the transcranial management of CPs, with acceptable endocrinological function and tumor-free survival. A decisive policy of open surgery with the objective of radical tumor removal remains a valid method for the primary treatment of CPs, aiming to avoid retreatment after tumor recurrence involving vital hypothalamic structures or hydrocephalus.