Background: Shift work is associated with many adverse effects on health and, in particular, affects sleep. In nurses, one of the most common forms of insomnia is shift work sleep disorder. Traditional face-to-face cognitive behavioral therapy for insomnia is often impractical for shift-working nurses due to irregular work schedules. Digital therapy presents a promising alternative to provide nurses with access to cognitive behavioral therapy for insomnia. Objective: To investigate the effectiveness of the digital SleepCare intervention for reducing insomnia in nurses being affected by shift work sleep disorder. Design: Randomized controlled trial. Participants: 74 nurses affected by shift work sleep disorder. Methods: In a two-armed randomized controlled trial, SleepCare was compared to shift work-specific psychoeducation published digitally by the German Sleep Society. The diagnosis of shift work sleep disorder was established through a clinical interview. The primary outcome was insomnia severity as measured by the Insomnia Severity Index at baseline before randomization, at 8 weeks, and 3 months after randomization. Further indicators of mental health and long-term hair cortisol concentration were evaluated as secondary endpoints. Results: Intention-to-treat analysis of covariance showed a greater reduction in insomnia severity in the intervention group versus psychoeducation, at both post-intervention (d = 1.11[0.7–1.6]) and follow-up (d = 0.97 [0.5–1.4]), corresponding to between-group differences of 5.0 and 5.3 points on the Insomnia Severity Index, respectively. 56 % completed at least five of the six sessions and results indicated larger effects for these intervention completers with d = 1.49 and d = 1.28, respectively. Statistically significant effects were observed for sleep-related, but not other mental health indicators, for example, stress and depression. Reduced hair cortisol levels were observed post-intervention in the SleepCare group (V = 82, p = .008; Δ = − 1.8 pg/mg, 44 % reduction from baseline). Conclusions: SleepCare was effective in reducing insomnia symptoms to a clinically meaningful extent and is one of the first digitally delivered programs to adapt cognitive behavioral therapy for insomnia with specific exercises to address nurses' needs for shift work. The development of effective strategies to promote treatment adherence seems necessary, as substantially larger effects were observed for intervention completers. Registration: German Clinical Trials Register – DRKS; DRKS00027411 (https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00027411). Registration date: March 9, 2022. Start of recruitment: May 13, 2022.