Background: Occupational hand eczema is common among hairdressers and implementing effective preventive measures requires a good understanding of the disease’s epidemiology. Objective: To investigate the long-term development of hand eczema (HE) in hairdressers. Methods: A prospective cohort study of all hairdressers graduating from Danish hairdressing vocational schools from 1985 to 2007 was conducted. A self-administered questionnaire was sent in 2009 with follow-up in 2020. Data from the Danish labour market supplementary pension scheme provided information on yearly affiliation with the hairdressing trade. Results: The cumulative lifetime prevalence of HE increased from 42.3% at baseline to 45.2% at follow-up (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0-1.2). The incidence rate decreased from 42.8 cases/1000 person-years (95% CI, 40.8–44.8) at baseline to 3.4 cases/1000 person-years (95% CI, 2.5–4.6) within the follow-up period. HE onset occurred within 8 years of beginning an apprenticeship for >90% of cases and occurred within the apprenticeship period for 68% of cases. The risk factors associated with having had HE at baseline were a previous positive patch test (adjusted OR [aOR], 5.3; 95% CI, 4.2–6.6), a history of atopic dermatitis (aOR, 3.4; 95% CI, 2.9–4.0) and female sex (aOR, 1.8; 95% CI 1.4–2.3). The most important risk factors at follow-up were previous HE (aOR, 10.1; 95% CI, 7.3–13.8) and a positive patch test within the follow-up period (aOR, 4.5; 95% CI, 3.0–6.8). Among the hairdressers who had HE at baseline, 65.5% exhibited remission, whereas 34.6% had persistent and often severe HE at follow-up. Hairdressers with persistent HE were the subgroup of the study population most frequently affected by the risk factors identified for HE. Conclusions: Primary prevention of HE should focus on hairdressing apprentices and fully trained hairdressers who have recently graduated. Approximately one-third of trained hairdressers develop persistent and often severe HE, emphasizing the need for early intervention.