Purpose: We aim to describe the characteristics of patients with childhood-onset craniopharyngioma and to analyze factors that impair quality of life (QoL) in this population. Methods: multicenter national study including patients treated between 2008-2022, from 2 to 25 years of age diagnosed with craniopharyngioma. QoL was assessed once during patient’s follow-up by age-adapted versions Pediatric Quality of Life Inventory (PedsQL TM) questionnaire. Results: Sixty-six patients were included. Median age at diagnosis was 5 years (IQR 3-8), while median follow-up was 7.4 years (IQR 2.8-9.7). Most craniopharyngioma were suprasellar (93.9%) and 59.7% had hypothalamic involvement (HI). All patients underwent surgery, 44.4% received radiotherapy and 23.6%, intra-cystic therapy. Most frequent long-term complications were visual deficit (72.7%) and endocrine impairment (94.5%). Patients exhibited hypothyroidism requiring hormone replacement (92.4%), hypocortisolism (80.3%), diabetes insipidus (86.4%) and/or growth hormone therapy (50%). When parents evaluated QoL, PedsQL TM median score was 53.8 points out of 100 (IQR 41-71.6). Higher scores were noted when patients assessed their own QoL [median-score 64.8 (IQR 57.3-81.8)], observing statistical-significant differences (p=0.019). QoL was impaired by repeated surgeries (r -0.44; p=0.014), HI [median-score 51.5 (IQR 39-63.8) vs 76.4 (59-84.8); p=0.001], radiotherapy [median-score 51.9 (IQR 38.1-61.3) vs 63.8 (IQR 49-82.5); p=0.02] and longer follow-up (r-0.3; p=0.01). Conclusion: In our study, most patients had significant comorbidities and low overall QoL scores, which was mainly affected by repeated surgery, radiation, and HI. The complex management of these patients requires multidisciplinary teams that can warrant the hypothalamic preservation and prompt intervention to prevent and identify sequelae.