<p>There is wide variability in intubation practice with lack of consensus regarding risks and benefits of nasal versus oral routes of intubation in children. We conducted a systematic review and meta-analysis comparing outcomes between oral and nasal intubation in children with cardiac disease. We searched PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials and Web of Science 10.23.2024. Methodology followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Meta-analysis for pooled estimates of effect was performed for data in patients ≤ 2 years if ≥ 3 studies examined the outcome with odds ratio (OR) and 95% confidence (CI) reported. Fifteen studies were identified, including 2 randomized control trials and 4 additional prospective studies. Seven studies were registry-based and 8 were single center analyses. Thirteen studies were included in the metanalysis. Four studies had low-risk of bias. Primary outcomes included intubation process and safety factors (<i>N</i> = 3,791 patients) and endotracheal tube security (<i>N</i> = 61,081). Secondary outcomes included extubation failure (<i>N = 11</i>,<i>779</i>) and oral feeding (<i>N</i> = 389). Oral intubation (versus nasal) was associated with greater pooled odds of severe adverse events [OR 2.82 (95%CI 1.24–6.40)], multiple intubation attempts [1.49 (95% CI:1.06–2.10)], unplanned extubation [OR 1.63 (95% CI 1.27–2.09)], and 37% greater median time to full oral feeds [OR 1.37 (95%CI 1.15–1.64)]. Conversely, oral intubation was associated with lower pooled odds of being unable to intubate [OR 0.06 (95% CI 0.01–0.46)]. Overall, nasal intubation is a reasonable and safe option with possibly improved outcomes in children ≤ 2 years with cardiac disease at centers with the expertise to place and manage nasal endotracheal tubes.</p>