Background: Congenital diaphragmatic hernia [CDH] is a life-threatening anomaly with a significant infant mortality rate. Few parameters have been well defined to aid in prediction of outcome of these infants. Objectives: This study was designed to report the characteristics of infants with congenital diaphragmatic hernia and their outcomes in relation to clinical, laboratory, and surgical findings. Methods: A 10 year retrospective cohort study of newborn infants with CDH in Aseer region was conducted. Results: A total of 21 cases of CDH were identified, male: female ratio was 1.6:1, 18 cases [86%] were left sided, 52% and 38% had low Apgar scores at 1 and 5 minutes, respectively, and 43% required high peak inspiratory pressure [>24cm H2O]. Initial blood gases done at the time of presentation showed acidosis [38%], hypoxia [71%], and hypercapnia [57%]. Associated anomalies were detected in 43% of cases in the form of congenital heart, gastrointestinal, and others. Stomach and viscera were present in the chest cavity of 38% and 33% of cases, respectively. Early surgical repair [<36 hours] was done for 33% of cases. Of all cases, 10 died, with a case fatality rate of 48%. Significant predictors of mortality were; hypercapnia [RR=6.75, 95% CI: 1.03-44.08], requirement of high peak inspiratory pressure [RR= 3.5, 95% CI: 1.27-9.65], and persistent pulmonary hypertension [RR= 2.13, 95% CI: 1.00-4.61]. Conclusion: Respiratory parameters such as arterial blood gases values, respiratory system compliance, ventilator settings, and respiratory complications may predict the outcome of infants with CDH.