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Class size reduction has been identified as a promising school mechanism to promote student achievement. Nonetheless, the findings produced by analyses of experimental and observational data in the U.S. have been mixed. In this study we used fourth grade data from PIRLS 2006 to examine the association between class size and reading achievement in the U.S. We used multilevel models to capture the nesting of the data. Overall, the results indicated a positive association between class size and reading achievement. Even when student background, teacher variables, and classroom composition and practices were included in the model, the class size estimate was positive and significant. We also observed a significant gender gap in reading that favored female students.