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The purpose of this experimental research study was to investigate effects of using Content Acquisition Podcasts (CAPs) to provide vocabulary instruction to adolescents with and without learning disabilities. CAPs are multimedia vignettes that deliver vocabulary instruction and adhere to design principles outlined by Mayer’s Cognitive Theory of Multimedia Learning. A total of 279 urban high school students, including 30 with LD, were randomly assigned to one of four experimental conditions with instruction occurring at individual computer terminals over a three-week period. Results indicated that students who received vocabulary instruction using CAPs with explicit instruction and the keyword mnemonic strategy significantly outperformed all other students who received only explicit or strategy instruction on measures of vocabulary knowledge.