BACKGROUND: Early pregnancy ultrasound scans are usually performed by nonexpert examiners in obstetrics/gynecology (OB/GYN) emergency departments. Establishing the precise diagnosis of pregnancy location is key for appropriate management of early pregnancies, and experts are usually able to locate a pregnancy in the first scan. A decision-support system based on a semantic, expert-validated knowledge base may improve the diagnostic performance of nonexpert examiners for early pregnancy transvaginal ultrasound. OBJECTIVE: This study aims to evaluate a novel Intelligent Scan Assistant System for early pregnancy ultrasound to diagnose the pregnancy location and determine the image quality. METHODS: Two trainees performed virtual transvaginal ultrasound examinations of early pregnancy cases with and without the system. The ultrasound images and reports were blindly reviewed by two experts using scoring methods. A diagnosis of pregnancy location and ultrasound image quality were compared between scans performed with and without the system. RESULTS: Each trainee performed a virtual vaginal examination for all 32 cases with and without use of the system. The analysis of the 128 resulting scans showed higher quality of the images (quality score: +23%; P<.001), less images per scan (4.6 vs 6.3 [without the CDSS]; P<.001), and higher confidence in reporting conclusions (trust score: +20%; P<.001) with use of the system. Further, use of the system cost an additional 8 minutes per scan. We observed a correct diagnosis of pregnancy location in 39 (61%) and 52 (81%) of 64 scans in the nonassisted mode and assisted mode, respectively. Additionally, an exact diagnosis (with precise ectopic location) was made in 30 (47%) and 49 (73%) of the 64 scans without and with use of the system, respectively. These differences in diagnostic performance (+20% for correct location diagnosis and +30% for exact diagnosis) were both statistically significant (P=.002 and P<.001, respectively). CONCLUSIONS: The Intelligent Scan Assistant System is based on an expert-validated knowledge base and demonstrates significant improvement in early pregnancy scanning, both in diagnostic performance (pregnancy location and precise diagnosis) and scan quality (selection of images, confidence, and image quality).