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Background: When the first piercing is failed to function, repeated puncturing imposes pain, complications, and delays the timeliness of pediatric care. In spite of the above challenges, incidence and predictors of first attempt peripheral intravenous cannulation failure are under-investigated in the study area and the nation at large.Objective: This study aimed to determine the incidence of first attempt peripheral intravenous cannulation failure and its predictors among children.Methods: Institution-based cross-sectional study design was conducted, and a total of 422 children were included in the study.The study participants were selected using a simple random sampling technique. The data were collected by direct observation and interviewer-administered questionnaire. Stata version 14 was used for analysis, and finally, the association was declared using AOR at a 95% confidence level at p≤0.05.Results: The incidence of first attempt peripheral intravenous cannulation failure rate was found to be 34.83% (132). Besides, self-payment funding, vein visibility with a tourniquet, forearm site, vein scope use, and child age of 24-59 months old were significantly associated with first attempt peripheral intravenous cannulation failure.Conclusion: Generally, self-payment funding, vein visibility with a tourniquet, forearm site, vein scope use, and child age of 24-59 months old were independent predictors of first attempt peripheral intravenous cannulation failure. Keywords: Peripheral IV cannulation; predictors; cross-sectional study