We evaluated the MULTILIT--"Making Up Lost Time in Literacy"--instruction program for individuals with Down syndrome. The 12-week program was administered on a 1:1 basis to participants who were assessed at three timepoints: Baseline, pre-instruction, and post-instruction. Participants were allocated non-randomly to two groups that had comparable abilities prior to intervention. These groups differed in the duration of the control period between baseline and pre-instruction: 12 weeks for Group 1 (n = 8, mean age = 168.88 months) and 24 weeks for Group 2 (n = 7, mean age = 164.71 months). Improvements in literacy skills were evaluated within participants (each participant serving as her/his own control), and the influence of control periods was evaluated between participants. Phonological awareness, word reading accuracy, and word spelling accuracy all improved significantly from pre- to post-instruction, with large effect sizes; whereas no statistically significant changes were observed during the control period (between baseline and pre-instruction assessments) regardless of the duration of this control period.