Background: Although previous studies have confirmed that Janus kinase (JAK) inhibitors have good efficacy and safety in the treatment of atopic dermatitis, the U.S. Food and Drug Administration has issued a black box warning for all JAKs. Therefore, it is necessary for us to further pay attention to their safety. Method: The medical literature data bases were searched from database creation until August 26, 2023. Randomized controlled trials of moderate-to-severe atopic dermatitis treated with JAK1-selective inhibitors (upadacitinib and abrocitinib) were included. Results: In this meta-analysis, which included 12 studies (one of which reported two outcomes), we collected data at 2, 4, 8, 12, and 16 weeks. Almost all results showed that JAK1-selective inhibitors were more efficacious than controls and had an onset of action at week 2. There was no significant difference in the incidence of serious adverse events and adverse events, leading to discontinuation, whereas, for treatment-associated adverse events, the JAK1-selective inhibitors were higher than the control group (RR 1.16 [95% confidence interval, 1.11‐1.21]; p < 0.00001). Conclusion: Overall, the treatment of atopic dermatitis with JAK1-selective inhibitors has a rapid onset of action. However, we need to be aware of the treatment-associated adverse events, more studies need to be conducted to provide better decisions on clinical medications for patients with moderate-to-severe atopic dermatitis.