Reaction time (RT) deficits are reported following concussion, but it is unknown when these deficits normalize to pre-injury status. It is also unclear how factors such as RT measurement technique and participant characteristics influence post-concussion RT. OBJECTIVE: The purpose of this systematic review and meta-analysis was to (1) characterize acute post-concussion (0-3 days) RT impairments, (2) examine RT recovery over time, and (3) explore moderating factors related to acute RT impairment following concussion. METHODS: Database searches (PubMed, CINAHL, EBSCOhost) were conducted according to PRISMA guidelines for articles published in English from January 2002 to March 2019. Studies compared baseline-to-post-injury RT within individuals (within-subject) and/or RT in concussed individuals to non-concussed controls (between-subject). Sixty studies met inclusion criteria, reporting on a total of 9688 participants with 214 discrete RT effects (Hedges’ d; between-subject: N = 29, k = 129; within-subject: N = 42, k = 85). Of the 214 effects, 93 occurred in the acute (0-3 days) post-injury timeframe (k = 47 between-subject). Numerous demographic [sex, age, concussion history, population type (athlete, military, and general population), athlete level (high school, college), and sport], and method-based (RT test and measure type, computerized neurocognitive testing platform, concussion definition, and time post-injury) moderators were examined for mean effect influence. Mixed-effects multi-level modeling with restricted-maximum-likelihood estimation was used to account for nested effects and high heterogeneity for the pooled effect size (D+). RESULTS: Significant medium-magnitude RT deficits were observed acutely for between- (D+ = – 0.7279, 95% CI – 0.9919, – 0.4639, I(2) = 88.66, p < 0.0001) and within-subject (D+ = - 0.7472, 95% CI - 0.9089, - 0.5855, I(2) = 89.21, p < 0.0001) effect models. RT deficits were present at the sub-acute and intermediate-term timeframes for between-subject effects (sub-acute: D+ = - 0.5655, 95% CI - 0.6958, - 0.4352, p < 0.0001; intermediate-term: D+ = - 0.3219, 95% CI - 0.5988, - 0.0450, p = 0.0245). No significant RT mean effect was observed for the between-subject model at the long-term timeframe, indicating RT recovery among concussed participants relative to controls (D+ = 0.3505, 95% CI - 0.4787, 1.1797, p = 0.3639). Sex was a significant moderator for between-subject effects, with every 1% male sample size increase demonstrating - 0.0171 (95% CI - 0.0312, - 0.0029, p = 0.0193) larger RT deficits. Within-subject effect models resulted in RT measure type (simple: [D+ = - 0.9826] vs. mixed: [D+ = - 0.6557], p = 0.0438) and computerized neurocognitive testing platforms (ANAM: [D+ = - 0.3735] vs. HeadMinder CRI: [D+ = - 1.4799] vs. ImPACT: [D+ = - 0.6749], p = 0.0004) having significantly different RT-deficit magnitudes. No other moderators produced significantly different RT-deficit magnitudes (between-subject: [p >/= 0.0763], within-subject: [p >/= 0.1723]). CONCLUSIONS: Robust RT deficits were observed acutely following concussion. Minimal magnitude differences were noted when comparing between- and within-subject effects, suggesting that pre-injury baselines may not add clinical value in determining post-injury RT impairment. RT deficits persisted up till the intermediate-term (21-59 days post-injury) timeframe and indicate lingering deficits exist. Mean effect size differences were observed between RT measure types and computerized neurocognitive testing platforms; however, all categories displayed negative effects consistent with impaired RT following concussion. Clinical interpretation suggests that measuring RT post-concussion is more important than considering the RT method employed so long as reliable and valid tools are used. PROSPERO Registration #CRD42019119323.