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Background: Intestinal failure (IF) is a broad term encompassing various conditions that hinder the body's ability to absorb nutrients for growth and maintenance. These conditions can significantly affect child's well-being, leading to physical limitations, psychological distress, and social isolation. We aimed to evaluate the available data on health-related quality of life (HRQoL) in pediatric patients with IF and without neurodevelopmental delay., Methods: For this systematic review and meta-analysis, we searched CINAHL, EMBASE, PsycINFO, PubMed, and Web of Science. All observational studies of pediatric patients (< 18 years) with IF which measured HRQOL and with evidence of absence of neurodevelopmental delay were included, without language or date restrictions, up to June 2024. We did separate random-effects meta-analyses for overall HRQOL and subgroup domains. Evidence from observational studies was synthesised as differences between standardised mean differences (SMDs) for all subgroup domains. Heterogeneity was assessed using the I² statistic and the Cochran Q test. The quality of the evidence was assessed with the Newcastle-Ottawa scale. This study is registered on PROSPERO, number CRD42024561812., Results: Of 491 records identified, 14 were eligible and data were available for 12 studies, all of which had a fair/good quality. The included studies involved a pooled sample of 510 participants (mean age = 7.0 ± 3.6 years). The analysis disclosed that compared to healthy children, pediatric patients with IF had lower overall quality of life in both child- and parent-report (Standardized Mean Difference [SMD]= -0.62; 95% CI [-0.80, -0.43]; p < 0.001, and SMD= -0.70; 95% CI [-1.11, -0.28]; p < 0.001, respectively), except for emotional and social domains (SMD[child] = -0.23; 95% CI [ -0.38, -0.08]; p = 0.001 Vs SMD[parent]= -0.23; 95% CI [ -0.60, 0.14]; p = 0.21, and SMD[child] = -0.40; 95% CI [ -0.70, -0.10]; p = 0.007 Vs SMD[parent]= -0.24; 95% CI [ -0.62, 0.14]; p = 0.21, respectively), where parents overestimate emotional and social HRQOL of their children., Conclusions: This study highlights the significant impact of IF on well-being of pediatric patients. Targeted interventions addressing both physical and psychosocial needs are crucial to improve HRQOL in this population., Competing Interests: Declarations. Human ethics and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)