Diaphragmatic paralysis (DP) in children can result from various etiologies. Guidelines for patient selection for diaphragmatic plication (DPL) are lacking. Our objectives were to describe the etiologies of DP and to determine the risk factors and predictors for DPL in the pediatric population. Retrospective data were retrieved from departmental databases on patients with DP from the pediatric, cardiac, and neonatal intensive care departments of Safra Children's Hospital from 2010 to 2017. DP was diagnosed in 88 patients, 29 with noncardiac surgery-related etiologies, for example, congenital, surgery, trauma, and shock and 59 with cardiac surgery-related etiologies. In total, 27 (31%) patients underwent DPL, and they had significant comorbidities involving respiratory, central nervous, and cardiovascular systems, higher lung injury scores, and lower weight compared with the patients who did not undergo DPL (P = .002, P = .002, P < .001, P = .012, and P = .013, respectively). A multivariate regression model revealed significant independent predictors for DPL, including morbidities of central nervous (odds ratio [OR = 9.651, P = .005), respiratory (OR = 4.875, P = .039), and cardiovascular systems (OR = 23.938, P = .001). Etiologies of DP are very diverse in the pediatric population. Comorbidities of respiratory, central nervous, and cardiovascular systems are risk factors for plication requirement in respiratory support-dependent pediatric patients with DP. Early DPL should be considered in these patients.