BACKGROUND Information about predictive factors of hand eczema is crucial for primary prevention. OBJECTIVE To investigate predictive factors of hand eczema in adult Danes from the general population. METHODS Participants from a cross-sectional 5-year follow-up study in the general population, aged 18-72 years (n = 2270), completed questionnaires about skin health and were grouped into four hand eczema groups: 'never', 'incident', 'nonpersistent' and 'persistent'. Multiple logistic regression models adjusted for age group and sex were used to evaluate associations with baseline variables. The participation rate for the follow-up study was 66·5% (29·7% of the participants originally invited to the baseline study). RESULTS A history of atopic dermatitis (AD) was associated with both persistent and incident hand eczema [odds ratio (OR) 9·0, 95% confidence interval (95% CI) 5·6-14·4 and OR 3·0, 95% CI 1·7-5·2, respectively]. Thus, even in adulthood, a history of AD should be considered as a predictor of incident hand eczema. While filaggrin gene (FLG) null mutations were not associated with incident hand eczema, a statistically significant association was observed with persistent hand eczema (OR 3·1, 95% CI 1·8-5·2). Finally, contact sensitization (23 allergens without nickel) was also associated with persistent hand eczema (OR 2·5, 95% CI 1·2-5·0), independently of a history of AD. CONCLUSIONS This study confirms a history of AD as the strongest predictor of persistent hand eczema. We additionally found that a history of AD was associated with incident hand eczema in adults, in contrast to FLG mutations, which were associated only with persistent hand eczema in individuals with a history of AD, and not with incident hand eczema. Our study adds new knowledge to the interplay between AD, FLG mutations and hand eczema in the adult general population.