Background: : Systemic immunosuppressive treatments are central in the treatment of severe atopic der- matitis (AD). Yet, comparative data are sparse on the performance of such immunosuppressive treatments in pediatric cohorts with severe AD. Objective: : This study aimed to examine the drug survival of systemic immunosuppressive treatments in a cohort of children with severe AD. Methods: : A retrospective pediatric cohort was identified using diagnosis and treatment codes registered in medical charts. In total, 135 cases were identified; of these, 36 were excluded. All information was obtained through examination of clinical records. Drug survival was analyzed with Kaplan–Meier plots, and a log-rank test was used to test for differences in drug survival. Results: : First-line treatment was primarily methotrexate (MTX; n = 63) and azathioprine (AZA; n = 32). For MTX, the drug survival rates were 69%, 50%, and 18% after 1, 2, and 4 years, respectively, with a me- dian drug survival time of 1.58 years. For AZA, these rates were 63%, 53%, and 21%, respectively, with a median drug survival time of 1.14 years. There was no significant difference in drug survival between the treatments. The main reason for discontinuation was adverse effects (MTX: 25%; AZA: 41%). Despite this, a majority of patients experienced a good effect at the moment of discontinuation or data-lock (MTX: 60%; AZA: 53%), and treatment effect assessed as improvement in sleep quality was highly sig- nificant ( p = .001). Second-line treatments included MTX (n = 12), AZA (n = 7), and cyclosporine (n = 5). These showed a median drug survival time of 1.8, 0.2, and 0.885 years, respectively. Conclusion: : MTX and AZA were the dominant first-line treatments prescribed and were safe and equally valuable treatment options for severe childhood AD with similar drug survival outcomes. MTX was the most used second-line treatment.