Objectives: To describe the mortality patterns, comorbidities, and attendance at accident and emergency departments among children with Down syndrome in Hong Kong. Study design: This is a population-based, retrospective cohort study of live births of children with Down syndrome delivered between 1995 and 2014, as identified from territory-wide hospitalization data in Hong Kong. The Kaplan-Meier product limit method was adopted to estimate the survival probabilities of children with Down syndrome by selected demographic and clinical characteristics. Cox regression analyses were conducted to examine associations of comorbidities and accident and emergency department accident and emergency departments attendances with mortality patterns. Results: There were 1010 live births of children with Down syndrome in Hong Kong within the study period and the average rate of live births with Down syndrome was 8.0 per 10 000 live births (95% CI, 6.8-9.30). The rate of live births with Down syndrome over the past 2 decades decreased from 11.8 per 10 000 live births in 1995 to 3.4 per 10 000 in 2014. Eighty-three patients with Down syndrome died during this period. The overall 6-month and 1- and 5-year survival probabilities were 95.8%, 94.4%, and 92.6%, respectively. There was a significant decrease in mortality rates over the study period, particularly among those born between 2000-2004 and 2005-2009 compared with those born between 1995 and 1999 (P < .05). Patients with Down syndrome without congenital cardiovascular anomalies and without low birth weight had lower mortality rates than those with these diagnoses. Conclusions: Over the past 2 decades, the early life mortality of children with Down syndrome in Hong Kong has improved significantly along with a reduction in Down syndrome live births.