Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain measures, including functional MRI (fMRI) and diffusion tensor imaging (DTI), can predict future long-term reading gains in dyslexia. No behavioral measure, including widely used and standardized reading and language tests, reliably predicted future reading gains in dyslexia. Greater right prefrontal activation during a reading task that demanded phonological awareness and right superior longitudinal fasciculus (including arcuate fasciculus) white-matter organization significantly predicted future reading gains in dyslexia. Multivariate pattern analysis (MVPA) of these two brain measures, using linear support vector machine (SVM) and cross-validation, predicted significantly above chance (72% accuracy) which particular child would or would not improve reading skills (behavioral measures were at chance). MVPA of whole-brain activation pattern during phonological processing predicted which children with dyslexia would improve reading skills 2.5 y later with >90% accuracy. These findings identify right prefrontal brain mechanisms that may be critical for reading improvement in dyslexia and that may differ from typical reading development. Brain measures that predict future behavioral outcomes (neuroprognosis) may be more accurate, in some cases, than available behavioral measures.inferior frontal gyrus | prediction | compensation | fractional anisotropy | rhyming D evelopmental dyslexia, which occurs in 5-17% of children, is a persistent difficulty in learning to read that is not explained by sensory deficits, cognitive deficits, lack of motivation, or lack of adequate reading instruction (1). Approximately one-fifth of individuals with developmental dyslexia manage to compensate for their underlying learning difficulties and develop adequate reading skills by the time they reach adulthood (2), but the mechanisms by which this compensation occurs remain largely unknown. Improved reading observed in developmental dyslexia is rarely complete, but instead refers to a level of reading superior to clinical cutoff scores that closes the gap between poor reader and typical readers, and that allows children to read adequately for purposes of learning. Many factors likely influence whether dyslexic children make substantial progress in reading, including access to educational resources and interventions, and neuropsychological and behavioral characteristics (reviewed in refs. 3 and 4), such as whether children have multiple deficits (e.g., in both rapid naming and phonological processing; ref. 5). A number of studies have examined neuropsychological, behavioral, and demographic predictors of developing dyslexia (e.g., refs. 6-8) and short-term response to intervention (RTI) (3, 4), but there is little evidence...