Neural tube defects (NTDs) are congenital anomalies of the central nervous system (CNS) which affects approximately one in every thousand pregnancies. The estimates, however, varies from country to country with countries implementing national programmes on folic acid fortification recording lower estimates. Neural tube defects are a common cause of morbidity and mortality especially in low-middle income countries such as Ghana. The study was conducted to determine the prevalence of neural tube defect and hydrocephalus in the only tertiary hospital in northern Ghana. This was a 4-year retrospective study from January 2010 to December 2014. Data regarding the age, sex, clinical diagnosis, and treatment outcomes were all retrieved from the registry of medical records using a simple data form designed for this study. During the study period, there were 35,426 deliveries at the facility with 57 cases of neural tube defects, thus giving a prevalence of 1.6 per 1000 births. They were more males than females with a male: female ratio of 2.4:1. All cases were diagnosed at birth. All the cases reported in this study were open neural tube defect (NTD). The most common defect was hydrocephalus occurring in 33 patients representing 57.9%, with spinal bifida occurring in 21 patients representing 38.6%. Encephalocele or cranium bifida occurred in only 5.3% (3 patients). Among the spinal bifida cases, myelomeningocele occurred in 13 patients (59.1%), with meningocele occurring in 8 patients (40.9%). Case fatality was about 15% of diagnosed cases. The prevalence of NTDs in this study is relatively high compared to earlier studies but, is consistent with other findings in the subregion. Prenatal screening and diagnosis are highly recommended since most women undergo routine ultrasonography as part of antenatal service.Journal of Medical and Biomedical Sciences (2017) 6(1), 18-23Keywords: neural tube defect, prevalence, spinal bifida, Northern Ghana