This study explored first-, second-, and third-grade reading instruction and students' (n = 1,586) reading skill growth in Florida Reading First (RF) classrooms (n = 95). The goal of RF is to improve students' literacy outcomes through the use of research-based instruction, assessment, teacher training, and program evaluation. Whereas survey data have shown that schools are generally implementing the major components of RF, we found no studies that related observed classroom instruction and student reading outcomes, which was the purpose of this study. Students attended schools that were historically high poverty with generally weak student achievement. Standardized assessments of vocabulary and reading comprehension, as well as progress-monitoring oral reading fluency tests, were administered. Classrooms were observed in the spring of the school year for 1 hour during reading instruction. In general, first graders demonstrated expected reading comprehension skills by the end of the school year; however, second and third graders did not. Hierarchical linear models revealed that the effect of instruction on students' reading comprehension was highly complex, varying substantially across grades. Further, the effect of instruction depended on the grade observed as well as students' vocabulary and fall oral reading fluency skills. (Contains 9 tables and 8 figures.)