Direct, explicit, and systematic instruction of critical skills has been a hallmark of effective teaching for many years. In this study, we implemented a quasi-experimental pre-/post-test design with nonequivalent groups to determine the effectiveness of syllable skills instruction on reading achievement. Participants included middle-school students with high incidence disabilities, including attention deficit hyperactivity disorder (ADHD) and their peers at risk for reading failure. The syllable skills intervention included instruction in syllable patterns, syllabication steps and rules, and accenting patterns. Students practiced skills by decoding and encoding nonsense and low-frequency mono- and multisyllabic words. Statistically significant differences were evident between pre-test and post-test scores for three dependent measures: (a) word identification, (b) word attack, and (c) reading comprehension. The treatment group demonstrated greater increase from pre-test to post-test on word identification, word attack, and reading comprehension; and the gap in fluency performance between the groups decreased. We discuss these outcomes with regard to their implications for practice and future research.