OBJECTIVE The aim of this study was to analyze the outcomes of transsphenoidal surgery (TSS) in a single-center clinical series of pediatric craniopharyngioma patients treated with gross-total resection (GTR). METHODS The authors retrospectively reviewed the surgical outcomes for 65 consecutive patients with childhood craniopharyngiomas (28 girls and 37 boys, mean age 9.6 years) treated with TSS (45 primary and 20 repeat surgeries) between 1990 and 2015. Tumors were classified as subdiaphragmatic or supradiaphragmatic. Demographic and clinical characteristics, including extent of resection, complications, incidence of recurrence, pre- and postoperative visual disturbance, pituitary function, and incidence of diabetes insipidus (DI), as well as new-onset obesity, were analyzed and compared between the primary surgeryand repeat surgery groups. RESULTS Of the 45 patients in the primary surgery group, 26 (58%) had subdiaphragmatic tumors and 19 had supradiaphragmatic tumors. Of the 20 patients in the repeat surgery group, 9 (45%) had subdiaphragmatic tumors and 11 had supradiaphragmatic tumors. The only statistically significant difference between the 2 surgical groups was in tumor size; tumors were larger (mean maximum diameter 30 mm) in the primary surgery group than in the repeat surgery group (25 mm) (p = 0.008). GTR was accomplished in 59 (91%) of the 65 cases; the GTR rate was higher in the primary surgery group than in the repeat surgery group (98% vs 75%, p = 0.009). Among the patients who underwent GTR, 12% experienced tumor recurrence, with a median follow-up of 7.8 years, and recurrence tended to occur less frequently in primary than in repeat surgery patients (7% vs 27%, p = 0.06). Of the 45 primary surgerypatients, 80% had deteriorated pituitary function and 83% developed DI, whereas 100% of the repeat surgery patients developed these conditions. Among patients with preoperative visual disturbance, vision improved in 62% but worsened in 11%. Visual improvement was more frequent in primary than in repeat surgery patients (71% vs 47%, p < 0.001), whereas visual deterioration was less frequent following primary surgery than repeat surgery (4% vs 24%, p = 0.04). Among the 57 patients without preoperative obesity, new-onset postoperative obesity was found in 9% of primary surgery patients and 21% of repeat surgery patients (p = 0.34) despite aggressive resection, suggesting that hypothalamic dysfunction was rarely associated with GTR by TSS in this series. However, obesity was found in 25% of the repeat surgerypatients preoperatively due to prior transcranial surgery. Although there were no perioperative deaths, there were complications in 12 cases (18%) (6 cases of CSF leaks, 3 cases of meningitis, 2 cases of transient memory disturbance, and 1 case of hydrocephalus). Postoperative CSF leakage appeared to be more common in repeat than in primary surgery patients (20% vs 4.4%, p = 0.2). CONCLUSIONS The results of TSS for pediatric craniopharyngioma in this case series suggest that GTR should be the goal for the first surgical attempt. GTR should be achievable without serious complications, although most patients require postoperative hormonal replacement. When GTR is not possible or tumor recurrence occurs after GTR, radiosurgery is recommended to prevent tumor regrowth or progression.