Background: Healthcare workers (HCWs) are at risk of developing hand dermatitis (HD). Guidelines recommend moisturizers to prevent HD, but in practice their effectiveness has been poorly investigated. Objectives: To assess whether an intervention aimed at improving skin care leads to a reduction in HD severity. Methods: In this 1-year randomized controlled trial, 9 wards (285 HCWs) were allocated to an intervention group (IG), and 10 wards (216 HCWs) were allocated to the control group (CG). The intervention included provision of cream dispensers with electronic monitoring of use, regularly communicated to the HCWs. The primary and secondary outcomes were change from baseline in Hand Eczema Severity Index (HECSI) score (ΔHECSI) and change in natural moisturizing factor (NMF) level (ΔNMF). Results: At 12 months, the rates of loss to follow-up were 41% and 39% in the IG and the CG, respectively. The HECSI score was reduced in the IG by −6.2 points (95%CI: −7.7 to −4.7) and in the CG by −4.2 points (95%CI: −6.0 to −2.4). There was no significant difference in ΔHECSI or ΔNMF between the groups. Relative improvement in the HECSI score was significantly higher in the IG than in the CG (56% vs 44%). In a subgroup of HCWs with mild HD, the IG showed a larger HECSI score decrease than the CG (P < 0.001). Conclusion: Although there was no significant effect on the primary outcomes, the intervention showed overall positive effects on the HECSI score.