Homophone confusion errors were examined in a series of 6 experiments. Across a variety of tasks, readers consistently made more errors on homophone trials than on control trials. These effects were established in Experiment 1 using a semantic-decision task in which participants judged whether pairs of words were related or unrelated. For both related and unrelated trials, error rates were higher for homophones as compared with controls. Results such as these have previously been taken as evidence for the role of phonology in lexical access and reading. However, differences in orthographic knowledge (more specifically, knowledge of spelling-to-meaning correspondences) across participants and homophone items significantly predicted homophone errors across all tasks. In addition, spelling tasks and multiple-choice questionnaires revealed differences in orthographic knowledge across participants and homophone items. Although these results do not rule out a role for phonology in lexical access, they indicate that homophone confusion errors may also be due to factors other than phonology.