We investigated the association between yes/no sentence comprehension and dysfunction in anterior and posterior left-hemisphere cortical regions in acute stroke patients. More specifically, we manipulated whether questions were Nonreversible (e.g., Are limes sour?) or Reversible (e.g., Is a horse larger than a dog?) to investigate the regions associated with semantic and syntactic processing. In addition, we administered lexical tasks (i.e., Picture-Word Verification, Picture Naming) to help determine the extent to which deficits in sentence processing were related to deficits in lexical processing. We found that errors on the lexical tasks were associated with ischemia in posterior-temporal Brodmann Areas (BA 21, 22, 37) and inferior parietal regions (BA 39, 40). Nonreversible question comprehension was associated with volume of tissue dysfunction, while Reversible question comprehension was associated with posterior regions (BA 39, 40) as well as one anterior region (BA 6). We conclude that deficits in Nonreversible questions required extensive dysfunction that affected language processing across multiple levels, while Reversible question comprehension was associated with regions involved in semantics as well as working memory that indirectly influenced syntactic processing. Overall, this suggests that yes/no question comprehension relies on multiple regions and that the importance of certain regions increases in relation to semantic, phonological, and syntactic complexity. (Contains 3 tables and 4 figures.)