The authors conducted a case-control study to determine whether risk factors for reading disability (RD) differentially affect boys and girls. The study population included all children born between 1976 and 1982 in Olmsted County, Minnesota (n = 5,701). A total of 303 RD cases were identified by using intelligence quotient and achievement test scores collected from school and medical records. After excluding those who met exclusion criteria (n = 869), controls consisted of all children not identified with RD (n = 4,529). The authors examined the association between RD and potential risk factors in boys and girls and confirmed their results in multivariable logistic regression models. Multivariable models indicated that girls of low birth weight were more than twice as likely to be identified as RD (odds ratio (OR) = 2.94, 95% confidence interval (CI): 1.09, 6.25). Girls whose mothers had 12 or fewer years of education were twice as likely to be identified as RD (OR = 2.14, 95% CI: 1.24, 3.72). However, girls whose fathers were aged 35 years or older at the time of birth were less likely to be identified as RD (OR = 0.24, 95% CI: 0.06, 0.92). Only 12 or fewer years of paternal education was associated with increased RD in boys (OR = 2.28, 95% CI: 1.59, 3.27). Boys and girls appear to be differentially susceptible to RD risk factors, suggesting that the biologic processes leading to RD may differ between boys and girls.