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Objective To compare the clinical characteristics between intrasuprasellar and suprasellar Rathke cleft cyst (RCC), and investigate the therapeutic efficacy of endoscopy for suprasellar RCC. Methods We retrospectively analyzed 61 intrasuprasellar and 15 suprasellar RCC treated by endoscopic endonasal approach (EEA) (standard or extended) in our hospital between January 2013 and August 2018. Their clinical manifestations, surgical conditions and outcomes were compared between the 2 groups. Results The cyst size was significantly smaller in suprasellar RCC than those in intrasuprasellar region (13.1±2.0 vs 17.5±4.2 mm, P < 0.001). The patients with suprasellar RCC were more commonly presented with visual loss, visual field defect and hyperprolactinemia than those with intrasuprasellar RCC (60.0% vs 27.9%; 66.7% vs 37.7%, P < 0.05). The duration of surgery and postoperative hospital stay were significantly longer in the suprasellar RCC group than the intrasuprasellar group (136±21 vs 106±33 min, P=0.001; 11.7±2.7 vs 5.8±3.1 d, both P < 0.001). The incidences of new- onset diabetes insipidus, intracranial infection and hyponatremia were obviously higher in the former group than the latter group (33.3% vs 8.2%, 20.0% vs 1.6%, 46.7% vs 14.8%, all P < 0.05). During the follow-up of 50.4±19.8 months, higher recurrence rate was observed in the suprasellar RCC group than the intrasuprasellar RCC group (26.7% vs 6.6%, P < 0.05). Conclusion Compared with intrasuprasellar RCC, suprasellar RCC, even though in smaller size, may present higher incidences of preoperative visual loss and field defect and hyperprolactinemia before operation, and more common new-onset diabetes insipidus, meningitis and hyponatremia postoperatively, as well as longer surgical period and hospital stay. Extended EEA is an effective and safe approach for the treatment of suprasellar RCC.