Background: During the past two decades there has been a sustained decline in child mortality; however, neonatal mortality has remained stagnant. Each year approximately 4 million babies are born asphyxiated resulting in 2 million neonatal deaths and intrapartum stillbirths. Almost all neonatal deaths occur in developing countries, where the majority is delivered at homes with negligible antenatal care and poor perinatal services. Objectives: To identify socio-demographic and clinical risk factors associated with birth asphyxia in Matiari District of Sindh Province, Pakistan. Method: A matched case control study was conducted in Matiari District with 246 cases and 492 controls. Newborn deaths with birth asphyxia diagnosed through verbal autopsy accreditation during 2005 and 2006 were taken as cases. Controls were the live births during the same period, matched on area of residence, gender and age. Result: The factors found to be associated with birth asphyxia mortality in Matiari District of Sindh Province, Pakistan are maternal education, history of stillbirths, pregnancy complications (including smelly or excessive vaginal discharge and anemia), intrapartum complications (including fever, prolong or difficult labour, breech delivery, cord around child’s neck, premature delivery, large baby size) and failure to establish spontaneous respiration after birth. Conclusion and Recommendation: There is an immediate need to develop strategies for early identification and management of factors associated with birth asphyxia by involving women, families, communities, community health workers, health professionals and policy makers. Community health workers should be trained for emergency obstetric care, basic newborn care including preliminary resuscitation measures to provide skilled birth attendance and encourage early recognition and referral.