Technology and the decreased cost of survey research have made it possible for researchers to collect data using new and varied modes of interview. These data are often analyzed as if they were generated using similar processes, but the modes of interview may produce differences in response simply due to the presence or absence of an interviewer. In this paper, we explore the differences in item non-response that result from different modes of interview and find that mode makes a difference. The data are from an experiment in which we randomly assigned an adult population to an in-person or self-completed survey after subjects agreed to participate in a short poll. For nearly every topic and format of question, we find less item non-response in the self-complete mode. Furthermore, we find the difference across modes in non-response is exacerbated for respondents with low levels of cognitive abilities. Moving from high to low levels of cognitive ability, an otherwise average respondent can be up to six times more likely to say “don’t know” in a face-to-face interview than in a self-completed survey, depending on the type of question.