Background: Cranial ultrasound is frequently performed in neonatal intensive care units and acquiring 2-dimensional (D) images requires significant training. Three-D ultrasound images can be acquired semi-automatically.Objective: This proof-of-concept study aimed to demonstrate that 3-D study image quality compares well with 2-D. If this is successful, 3-D images could be acquired in remote areas and read remotely by experts.Materials and methods: This was a prospective study of 20 neonates, who underwent both routine 2-D and 3-D cranial ultrasounds. Images were reconstructed into standard views extracted from the 3-D volume and evaluated by three radiologists blinded to the acquisition method. The radiologists assessed for the presence of anatomical landmarks and overall image quality.Results: More anatomical structures were identified in the 3-D studies (P<0.01). There was a trend that 3-D ultrasound demonstrated better image quality in the coronal plane, and 2-D in the sagittal plane, only reaching statistical significance for two coronal views and two sagittal views.Conclusion: Overall, this study has demonstrated that 3-D cranial ultrasound performs similarly to 2-D and could be implemented into neonatal practice.