Cardiopulmonary resuscitation (CPR) training for adolescents is a prominent strategy to increase the number of community first responders who can recognize cardiac arrest and initiate CPR. More schools are adopting technology-based CPR training modalities to reduce class time and reliance on instructor availability and increase their capacity for wider training dissemination. However, it remains unclear whether these technology-based modalities are comparable with standard training. This study aimed to systematically review and perform meta-analyses to evaluate the effectiveness of technology-based CPR training on adolescents' CPR skills and knowledge. Searches were conducted in PubMed, Embase, Cochrane Library, Ovid MEDLINE, CINAHL, PsycINFO, Education Resources Information Center, ProQuest Dissertations and Theses Global, and Scopus from inception to June 25, 2021. Eligible randomized controlled trials (RCTs) compared technology-based training with standard training for adolescents aged 12 to 18 years. Studies were appraised using the Cochrane risk-of-bias tool. Random-effects meta-analyses were performed using Review Manager (The Cochrane Collaboration). Subgroup analyses were conducted to explore sources of heterogeneity. Overall certainty of evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventeen RCTs involving 5578 adolescents were included. Most of the studies had unclear risks of selection bias (9/17, 53%) and high risks of performance bias (16/17, 94%). Interventions that included instructor guidance increased the likelihood of adolescents checking the responsiveness of the person experiencing cardiac arrest (risk ratio 1.39, 95% CI 1.19-1.63) and calling the emergency medical services (risk ratio 1.11, 95% CI 1.00-1.24). Self-directed technology-based CPR training without instructor guidance was associated with poorer overall skill performance (Cohen d=-0.74, 95% CI -1.02 to -0.45). Training without hands-on practice increased mean compression rates (mean difference 9.38, 95% CI 5.75-13.01), whereas real-time feedback potentially yielded slower compression rates. Instructor-guided training with hands-on practice (Cohen d=0.45, 95% CI 0.13-0.78) and the use of computer programs or mobile apps (Cohen d=0.62, 95% CI 0.37-0.86) improved knowledge scores. However, certainty of evidence was very low. Instructor-guided technology-based CPR training that includes hands-on practice and real-time feedback is noninferior to standard training in CPR skills and knowledge among adolescents. Our findings supported the use of technology-based components such as videos, computer programs, or mobile apps for self-directed theoretical instruction. However, instructor guidance, hands-on practice, and real-time feedback are still necessary components of training to achieve better learning outcomes for adolescents. Such a blended learning approach may reduce class time and reliance on instructor availability. Because of the high heterogeneity of the studies reviewed, the findings from this study should be interpreted with caution. More high-quality RCTs with large sample sizes and follow-up data are needed. Finally, technology-based training can be considered a routine refresher training modality in schools for future research.