AimsThe 2010 European Society of Cardiology (ESC) guidelines for electrocardiogram (ECG) interpretation in athletes are associated with a relatively high false positive rate and warrant modification to improve the specificity without compromising sensitivity. The aim of this study was to investigate whether non-specific anomalies such as axis deviation and atrial enlargement in isolation require further assessment in highly trained young athletes.Method and resultsBetween 2003 and 2011, 2533 athletes aged 14-35 years were investigated with 12-lead ECG and echocardiography. Electrocardiograms were analysed for non-training-related (Group 2) changes according to the 2010 ESC guidelines. Results were compared with 9997 asymptomatic controls. Of the 2533 athletes, 329 (13%) showed Group 2 ECG changes. Isolated axis deviation and isolated atrial enlargement comprised 42.6% of all Group 2 changes. Athletes revealed a slightly higher prevalence of these anomalies compared with controls (5.5 vs. 4.4%; P = 0.023). Echocardiographic evaluation of athletes and controls with isolated axis deviation or atrial enlargement (n = 579) failed to identify any major structural or functional abnormalities. Exclusion of axis deviation or atrial enlargement reduced the false positive rate from 13 to 7.5% and improved specificity from 90 to 94% with a minimal reduction in sensitivity (91-89.5%).ConclusionIsolated axis deviation and atrial enlargement comprise a high burden of Group 2 changes in athletes and do not predict underlying structural cardiac disease. Exclusion of these anomalies from current ESC guidelines would improve specificity and cost-effectiveness of pre-participation screening with ECG.