Background: Screening for cardiovascular disease (CVD) and its associated risk factors in childhood facilitates early detection and timely preventive interventions. However, limited data are available regarding screening tools and their diagnostic yield when applied in unselected pediatric populations. Aims: To evaluate the performance of a CVD screening program, based on history, 12-lead ECG and phonocardiography, applied in primary school children. Methods: The methods used were prospective study, with voluntary participation of third-grade primary school children in the region of Crete/Greece, over 6 years (2018–2024). Personal and family history were collected by using a standardized questionnaire and physical evaluation (including weight, height, blood pressure measurement), and cardiac auscultation (digital phonocardiography (PCG)) and 12-lead electrocardiogram (ECG) were recorded at local health stations (Phase I). Following expert verification of responses and obtained data, assisted by designated electronic health record with incorporated decision support algorithms (phase II), pediatric cardiology evaluation at the tertiary referral center followed (phase III). Results: A total of 944 children participated (boys 49.6%). A total of 790 (83.7%) had Phase I referral indication, confirmed in 311(32.9%) during Phase II evaluation. Adiposity (10.8%) and hypertension (3.2%) as risk factors for CVD were documented in 10.8% and 3.2% of the total population, respectively. During Phase III evaluations (n = 201), the majority (n = 132, 14% of total) of children were considered as having a further indication for evaluation by other pediatric subspecialties for their reported symptoms. Abnormal CVD findings were present in 69 (7.3%) of the study population, including minor/trivial structural heart disease in 23 (2.4%) and 17 (1.8%), respectively, referred due to abnormal cardiac auscultation, and ECG abnormalities in 29 (3%), of which 6 (0.6%) were considered potentially significant (including 1 case of genetically confirmed channelopathy-LQT syndrome). Conclusions: CVD screening programs in school children can be very helpful for the early detection of CVD risk factors and of their general health as well. Expert cardiac auscultation and 12-lead ECG allow for the detection of structural and arrhythmogenic heard disease, respectively. Further study is needed regarding performance of individual components, accuracy of interpretation (including computer assisted diagnosis) and cost-effectiveness, before large-scale application of CVD screening in unselected pediatric populations.