Introduction: Second-trimester fetal screening for congenital heart defects (CHD) included in routine obstetric care provides relevant information for decision making. The aim of this study was to describe the clinical practice of prenatal detection of CHD in terms of the process and results. Methods: The characteristics and results of ultrasound screening for major CHD were documented using data provided by hospitals for a national survey in Spain over the period of 2004–2006. Sixty-seven percent of eligible centers (56/83), covering 36% of total births nationwide, responded to the survey; 33 of these returned complete data regarding the screening results. Results: The number of major CHD occurring in the centers which provided data with results of screening was 1,060. The overall prenatal detection rate of major CHD was 65.7% (95% CI 57.8–74.7), but the detection rate in the routine second-trimester scan was 52.6% (95% CI 45.6–60.8). In 61% of these cases the parents chose to terminate the pregnancy. Two independent predictors of increased detection by center were identified: first, the uniformity and systematic character of the examination of the heart showing at least the 4-chamber view and outflow tracts (prevalence ratio 1.3, 95% CI 1.0–1.8) and second, the local availability of specialists in fetal echocardiography (prevalence ratio 1.4, 95% CI 1.1–1.9). Conclusions: The detection of major CHD in the first half of pregnancy has an important impact on parental decision making. The prenatal screening program for CHD should be globally strengthened in terms of qualifications and methodological approaches. To improve its performance locally, close collaboration with fetal heart specialists should be promoted.