Background: Organisational and individual factors cause strain in the daily lives of nurses and other healthcare professionals, who have a high prevalence of stress-related disorders. Accordingly, there is a strong need for integrated occupational health promotion interventions that include both work-directed and person-directed interventions. The psychosocial safety climate is seen as an overarching occupational health objective and can potentially be improved by implementing integrated mental health interventions. Objective: Following an integrated approach, we developed an occupational e-mental health platform, Care4Care, which integrates both work- and person-directed interventions for promoting mental health in nurses. We evaluated the effects of the platform compared with those of an extended care-as-usual control condition. Design: Clustered randomised controlled trial. Setting: Healthcare service facilities in Germany nationwide. Participants: 347 nursing staff members (intervention: 211, control: 136) from 33 healthcare service facilities. Methods: The participants received either immediate access to the platform or access to two short subcomponents of the platform plus routine occupational health promotion offerings as well as delayed access to the whole platform after 6 months. The primary outcome was improvement in the psychosocial safety climate after 6 months. The secondary outcomes included perceived stress, depressive symptoms, and other strain-related indicators. Results: Bayesian multilevel analyses revealed an improvement of approximately 2 points (Cohen's d = 0.25) in the psychosocial safety climate in the intervention group compared with the control group. Applying a 95 % credible interval, this effect contained zero (− 0.32, 4.44), which indicated uncertainty about the effectiveness of the intervention on the psychosocial safety climate. The analyses of the secondary outcomes revealed effects in the expected direction with high credibility for a decreasing effect on perceived stress and considerable uncertainty with regard to all other secondary and tertiary outcomes. A total of 85 (40 %) participants in the intervention group used Care4Care, whereas 37 (27 %) participants in the control group used the two subcomponents of the platform. Conclusions: This study highlights the potential of an occupational e-mental health platform that combines work- and person-directed interventions with face-to-face components for nursing staff. The findings emphasise the necessity of conducting more in-depth implementation studies to identify the factors that facilitate the successful implementation and uptake of occupational e-mental health platforms. Registration: German Clinical Trials Register – DRKS (DRKS00027869). Registration date: February 23, 2022. Start of recruitment: June 21, 2022.