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This systematic review and meta-analysis examines the overall effect of synchronous online learning on cognitive and affective educational outcomes, while using asynchronous online learning or face-to-face learning as the control groups. Following a systematic identification and screening procedure, we identified 19 publications with 27 independent effect sizes published between 2000 and 2019. Overall, there was a statistically significant small effect in favor of synchronous online learning versus asynchronous online learning for cognitive outcomes. However, the other models were not statistically significant. The effect size data was normally distributed and were significantly moderated by course duration, instructional method, student equivalence, learner level, and discipline. Implications for educational practice and research are included.