Using the meta-analysis technique, this research comprehensively reviews the existing open innovation (OI) literature, systematically aggregates empirical findings on the impact of OI on performance to identify key moderators and statistically tests the significance of these moderators in influencing the OI–performance relationship. Based on a comprehensive dataset of 2,377,123 firms and sub-firm units in 171 studies published from 2003 to 2018, this research demonstrates that the OI–performance relationship is significantly moderated by three key factors: performance measure, OI approach, and level of analysis. This research helps explain the conflicting findings regarding the OI–performance relationship in the existing literature, and contributes to the understanding of the effectiveness of OI practice.