Objectives: The main aim of this study was to assess the proportion and type of congenital anomalies, both structural and chromosomal, that can be detected at an early scan performed at 12–13 weeks' gestation, compared with at the 20-week structural anomaly scan offered under the present screening policy. Secondary aims were to evaluate the incidence of false-positive findings and ultrasound markers at both scans, and parental choice regarding termination of pregnancy (TOP). Methods: Sonographers accredited for nuchal translucency (NT) measurement were asked to participate in the study after undergoing additional training to improve their skills in late first-trimester fetal anatomy examination. The early scans were performed according to a structured protocol, in six ultrasound practices and two referral centers in the north-east of The Netherlands. All women opting for the combined test (CT) or with an increased a-priori risk of fetal anomalies were offered a scan at 12–13 weeks' gestation (study group). All women with a continuing pregnancy were offered, as part of the ‘usual care’, a 20-week anomaly scan. Results: The study group consisted of 5237 women opting for the CT and 297 women with an increased a-priori risk of anomalies (total, 5534). In total, 51 structural and 34 chromosomal anomalies were detected prenatally in the study population, and 18 additional structural anomalies were detected after birth. Overall, 54/85 (63.5%) anomalies were detected at the early scan (23/51 (45.1%) structural and all chromosomal anomalies presenting with either an increased risk at first-trimester screening or structural anomalies (31/34)). All particularly severe anomalies were detected at the early scan (all cases of neural tube defect, omphalocele, megacystis, and multiple severe congenital and severe skeletal anomalies). NT was increased in 12/23 (52.2%) cases of structural anomaly detected at the early scan. Of the 12 cases of heart defects, four (33.3%) were detected at the early scan, five (41.7%) at the 20-week scan and three (25.0%) after birth. False-positive diagnoses at the early scan and at the 20-week scan occurred in 0.1% and 0.6% of cases, respectively, whereas ultrasound markers were detected in 1.4% and 3.0% of cases, respectively. After first- or second-trimester diagnosis of an anomaly, parents elected TOP in 83.3% and 25.8% of cases, respectively. Conclusions: An early scan performed at 12–13 weeks' gestation by a competent sonographer can detect about half of the prenatally detectable structural anomalies and 100% of those expected to be detected at this stage. Particularly severe anomalies, often causing parents to choose TOP, are amenable to early diagnosis. The early scan is an essential part of modern pregnancy care.