Background: In high-resource settings, obstetric ultrasound is a standard component of prenatal care used to identify pregnancy complications and to establish an accurate gestational age in order to improve obstetric care. Whether or not ultrasound use will improve care and ultimately pregnancy outcomes in low-resource settings is unknown.Methods/Design: This multi-country cluster randomized trial will assess the impact of antenatal ultrasound screening performed by health care staff on a composite outcome consisting of maternal mortality and maternal near-miss, stillbirth and neonatal mortality in low-resource community settings. The trial will utilize an existing research infrastructure, the Global Network for Women's and Children's Health Research with sites in Pakistan, Kenya, Zambia, Democratic Republic of Congo and Guatemala. A maternal and newborn health registry in defined geographic areas which documents all pregnancies and their outcomes to 6 weeks post-delivery will provide population-based rates of maternal mortality and morbidity, stillbirth, neonatal mortality and morbidity, and health care utilization for study clusters. A total of 58 study clusters each with a health center and about 500 births per year will be randomized (29 intervention and 29 control). The intervention includes training of health workers (e.g., nurses, midwives, clinical officers) to perform ultrasound examinations during antenatal care, generally at 18-22 and at 32-36 weeks for each subject. Women who are identified as having a complication of pregnancy will be referred to a hospital for appropriate care. Finally, the intervention includes community sensitization activities to inform women and their families of the availability of ultrasound at the antenatal care clinic and training in emergency obstetric and neonatal care at referral facilities.Discussion: In summary, our trial will evaluate whether introduction of ultrasound during antenatal care improves pregnancy outcomes in rural, low-resource settings. The intervention includes training for ultrasound-naïve providers in basic obstetric ultrasonography and then enabling these trainees to use ultrasound to screen for pregnancy complications in primary antenatal care clinics and to refer appropriately. Trial registration: Clinicaltrials.gov (NCT # 01990625). © 2014 McClure et al.; licensee BioMed Central Ltd.