Objective: To describe incidence of Down syndrome in Dubai, United Arab Emirates (UAE). Subjects and Methods: A total of 63,398 newborn babies in Dubai (24,250 UAE nationals and 39,148 non-UAE) during a 5-year period of 1999–2003 were routinely examined by experienced nurses, neonatologists, pediatricians and/or general practitioners for symptoms of Down syndrome. Those suspected with Down syndrome were referred to the cytogenetic laboratory for karyotyping. Results: A total of 141 cases were confirmed cytogenetically as Down syndrome. Of these, 139 were trisomy 21 and of the remaining 2, 1 was a translocation and the other a mosaic. Theoverall incidence of Down syndrome in Dubai was 1/449 live births (2.2 per 1,000); 1/319 live births (3.13 per 1,000) among UAE nationals and 1/602 live births (1.66 per 1,000) among non-UAE nationals. The mean maternal age of UAE national mothers was 33.48 ± 8.08, with 41.66% of the mothers being in the advanced maternal age group (>35 years). The higher incidence of Down syndrome among UAE nationals is comparable to incidences reported for other Arab populations in the Middle Eastern region. Advanced maternal age, with mothers bearing children until their 50s and higher parity, appear to be the major contributing factors for the increased incidence. Conclusion: The study indicates the need to provide efficient genetic counseling and to introduce an effective antenatal screening program and prenatal diagnostic services to reduce the psychological and genetic burden on the families and community.