Objectives Major ECG abnormalities have been associated with increased risk of cardiovascular disease (CVD) burden in asymptomatic populations. However, sex differences in occurrence of major ECG abnormalities have been poorly studied, particularly across ethnic groups. The objectives were to investigate (1) sex differences in the prevalence of major and, as a secondary outcome, minor ECG abnormalities, (2) whether patterns of sex differences varied across ethnic groups, by age and (3) to what extent conventional cardiovascular risk factors contributed to observed sex differences. Design Cross-sectional analysis of population-based study. Setting Multi-ethnic, population-based Healthy Life in an Urban Setting cohort, Amsterdam, the Netherlands. Participants 8089 men and 11 369 women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin aged 18–70 years without CVD. Outcome measures Age-adjusted and multivariable logistic regression analyses were performed to study sex differences in prevalence of major and, as secondary outcome, minor ECG abnormalities in the overall population, across ethnic groups and by age-groups (18–35, 36–50 and >50 years). Results Major and minor ECG abnormalities were less prevalent in women than men (4.6% vs 6.6% and 23.8% vs 39.8%, respectively). After adjustment for conventional risk factors, sex differences in major abnormalities were smaller in ethnic minority groups (OR ranged from 0.61 in Moroccans to 1.32 in South-Asian Surinamese) than in the Dutch (OR 0.49; 95% CI 0.36 to 0.65). Only in South-Asian Surinamese, women did not have a lower odds than men (OR 1.32; 95% CI 0.96 to 1.84). The pattern of smaller sex differences in ethnic minority groups was more pronounced in older than in younger age-groups. Conclusions The prevalence of major ECG abnormalities was lower in women than men. However, sex differences were less apparent in ethnic minority groups. Conventional risk factors did not contribute substantially to observed sex differences.