Lie detection techniques are frequently used, but most of them have been criticized for the lack of empirical support for their predictive validity and presumed underlying mechanisms. This situation has led to increased efforts to unravel the cognitive mechanisms underlying deception and to develop a comprehensive theory of deception. A cognitive approach to deception has reinvigorated interest in reaction time (RT) measures to differentiate lies from truths and to investigate whether lying is more cognitively demanding than truth telling. Here, we provide the results of a meta-analysis of 114 studies (n = 3307) using computerized RT paradigms to assess the cognitive cost of lying. Results revealed a large standardized RT difference, even after correction for publication bias (d = 1.049; 95% CI [0.930; 1.169]), with a large heterogeneity amongst effect sizes. Moderator analyses revealed that the RT deception effect was smaller, yet still large, in studies in which participants received instructions to avoid detection. The autobiographical Implicit Association Test produced smaller effects than the Concealed Information Test, the Sheffield Lie Test, and the Differentiation of Deception paradigm. An additional meta-analysis (17 studies, n = 348) showed that, like other deception measures, RT deception measures are susceptible to countermeasures. Whereas our meta-analysis corroborates current cognitive approaches to deception, the observed heterogeneity calls for further research on the boundary conditions of the cognitive cost of deception. RT-based measures of deception may have potential in applied settings, but countermeasures remain an important challenge.