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In flipped instruction (FI), students watch lessons at home and deepen their engagement with and knowledge of topics through constructivist teaching practices in class. This meta-analysis investigates the effect of FI on college students’ learning in STEM subject domains. Based on 73 empirical studies that met all inclusion criteria, findings show that FI is effective for learning STEM subjects (g = 0.32, SE = 0.07, 95% CI = [0.19, 0.46]. Due to high heterogeneity of effect sizes, moderator analyses were conducted. The results show that pre-class instructional features, structure of in-class activities, treatment duration, country of study, and STEM subject domains significantly moderate the effects of FI. The implications of these findings for designing and implementing FI are discussed.