Background: Insomnia is a prevalent condition with significant health, societal, and economic impacts. Cognitive behavioral therapy for insomnia (CBTI) is recommended as the first-line treatment. With limited accessibility to in-person-delivered CBTI (ipCBTI), electronically delivered eHealth CBTI (eCBTI), ranging from telephone- and videoconference-delivered interventions to fully automated web-based programs and mobile apps, has emerged as an alternative. However, the relative efficacy of eCBTI compared to ipCBTI has not been conclusively determined., Objective: This study aims to test the comparability of eCBTI and ipCBTI through a systematic review and meta-analysis of equivalence based on randomized controlled trials directly comparing the 2 delivery formats., Methods: A comprehensive search across multiple databases was conducted, leading to the identification and analysis of 15 unique randomized head-to-head comparisons of ipCBTI and eCBTI. Data on sleep and nonsleep outcomes were extracted and subjected to both conventional meta-analytical methods and equivalence testing based on predetermined equivalence margins derived from previously suggested minimal important differences. Supplementary Bayesian analyses were conducted to determine the strength of the available evidence., Results: The meta-analysis included 15 studies with a total of 1083 participants. Conventional comparisons generally favored ipCBTI. However, the effect sizes were small, and the 2 delivery formats were statistically significantly equivalent (P<.05) for most sleep and nonsleep outcomes. Additional within-group analyses showed that both formats led to statistically significant improvements (P<.05) in insomnia severity; sleep quality; and secondary outcomes such as fatigue, anxiety, and depression. Heterogeneity analyses highlighted the role of treatment duration and dropout rates as potential moderators of the differences in treatment efficacy., Conclusions: eCBTI and ipCBTI were found to be statistically significantly equivalent for treating insomnia for most examined outcomes, indicating eCBTI as a clinically relevant alternative to ipCBTI. This supports the expansion of eCBTI as a viable option to increase accessibility to effective insomnia treatment. Nonetheless, further research is needed to address the limitations noted, including the high risk of bias in some studies and the potential impact of treatment duration and dropout rates on efficacy., Trial Registration: PROSPERO CRD42023390811; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=390811., (©Sofie Møgelberg Knutzen, Dinne Skjærlund Christensen, Patrick Cairns, Malene Flensborg Damholdt, Ali Amidi, Robert Zachariae. Originally published in JMIR Mental Health (https://mental.jmir.org), 26.08.2024.)