Purpose To compare automated breast volumetric scanning (ABVS) with hand-held bilateral whole breast ultrasound (HHUS) prospectively in regards to patient workflow, woman preference, efficacy in lesion detection, and characterization. Materials and methods Supplemental screening was performed with both ABVS and HHUS to 345 women with dense breasts and negative mammograms. Acquisition and evaluation times were recorded. Lesions were classified according to BIRADS US criteria and compared one to one. Women were recalled for a secondary HHUS examination if ABVS showed any additional lesions. Findings were compared based on biopsy results and/or 36-48 months of follow-up. Results Findings could be compared for 340 women. There were two carcinomas which were detected by both methods, with no interval cancers in the follow-up period. Recall rate was 46/340 (13.05%) for ABVS and 4/340 (1.18%) for HHUS. ABVS recalls decreased with experience. HHUS had more true negative (BIRADS 1-2) results, while ABVS had more false positive ones (p < 0.001). Positive predictive value was 4.17% for ABVS and 50% for HHUS. ABVS overdiagnosed shadowings (p < 0.01), distortions (p < 0.034), and irregular nodules (p < 0.001) in comparison to HHUS. At ABVS, 10.6% of women experienced severe pain. 59.7% stated that they would choose HHUS if they had the chance. Conclusion ABVS is as good as HHUS in lesion detection. However, the recall rate is higher and positive predictive value is lower with ABVS, which could result in more follow-ups, and more anxiety for the women. More than 50% women stated they would prefer HHUS if they were given the chance.