In a randomized control trial, the authors tested whether short- and long-term effects of an early literacy intervention are moderated by mild perinatal adversities in accordance with differential susceptibility theory. One-hundred 5-year-old children (58% male) who scored at or below the 30th percentile on early literacy measures were randomized to a Web-based remedial early literacy program Living Letters or a treated control group. Parents gave written informed consent to access the perinatal data of their children at the Perinatal Register in the Netherlands. Twenty-one children were, at birth, small for gestational age (between the 2.5th and 10th percentiles) or late preterm (between 34 and 37 weeks, 6 days). In this group with mild perinatal adversities, intervention children outperformed the control group immediately after the intervention and after 8 months of formal reading instruction, but a similar effect of the computerized literacy program in children without mild perinatal adversities was absent. In line with the theory of differential susceptibility, children with mild perinatal adversities seem to be more open to environmental input, for better "and" for worse. (Contains 1 figure, 5 tables, and 2 footnotes.)