Over the past decade, parent advocacy groups led a grass-roots movement resulting in most states adopting dyslexia-specific legislation, with many states mandating the use of the Orton-Gillingham approach to reading instruction. Orton-Gillingham is a direct, explicit, multisensory, structured, sequential, diagnostic, and prescriptive approach to reading for students with or at-risk for world-level reading disabilities (WLRD). Evidence from a prior synthesis (Ritchey & Goeke, 2006) and What Works Clearinghouse reports (WWC, 2010) yielded findings lacking support for the effectiveness of Orton-Gillingham interventions. We conducted a meta-analysis to examine the effects of Orton-Gillingham reading interventions on the reading outcomes of students with or at risk for WLRD. Findings suggested Orton-Gillingham reading interventions do not statistically significantly improve foundational skill outcomes (i.e., phonological awareness, phonics, fluency, spelling; ES = 0.22, p = .40); though the mean effect size was positive in favor of Orton-Gillingham-based approaches. Similarly, there were not significant differences for vocabulary and comprehension outcomes (ES = 0.14; p = .59) for students with or at-risk for WLRD. More high quality, rigorous research with larger samples of students with WLRD is needed to fully understand the effects of Orton-Gillingham interventions on the reading outcomes for this population.