The study explored the total, direct and indirect effects of emotion knowledge on adjustment in preschoolers and examined whether emotion regulation mediated the relationships between emotion knowledge and adjustment (social competence, and behavioral difficulties, such as anxiety-withdrawal and anger-aggression). Two hundred forty children (118 boys and 122 girls) from 3 to 5 years of age (mean age = 4.23, SD = .80) were administered a vocabulary test to check their verbal ability and a measure of emotion knowledge. Teachers filled out two questionnaires about children's regulation and adjustment variables. A mediation model was tested combined with an assessment of the indirect effects to evaluate whether emotion knowledge may exert an influence on adjustment through the intervention of emotion regulation. Results showed that all conditions for full mediation were met for social competence and anxiety-withdrawal, confirming the mediation role of emotion regulation in the relationship between emotion knowledge and these variables. Moreover, results indicated that emotion knowledge and anger-aggression were not directly associated as they would be in case of full or partial mediation, but they were however indirectly related through a significant linking with emotion regulation. Findings may have potential implications for prevention and intervention programs in family and school contexts, suggesting how early childhood programs targeting emotion knowledge may be especially beneficial to promote social competence and prevent behavioral problems, above all if they include other emotion-related competences, such as emotion regulation, that may be considered the linking mechanism through which emotion knowledge exerts an influence on adjustment. (author abstract)