Background In the midst of rapid expansion of medical knowledge and decision-support tools intended to benefit diverse patients, patients with limited health literacy (the ability to obtain, process, and understand information and services to make health decisions) will benefit from asking questions and engaging actively in their own care. But little is known regarding the relationship between health literacy and question-asking behavior during outpatient office visits. Questions/purposes (1) Do patients with lower levels of health literacy ask fewer questions in general, and as stratified by types of questions? (2) What other patient characteristics are associated with the number of questions asked? (3) How often do surgeons prompt patients to ask questions during an office visit? Methods We audio-recorded office visits of 84 patients visiting one of three orthopaedic hand surgeons for the first time. Patient questions were counted and coded using an adaptation of the Roter Interaction Analysis System in 11 categories: (1) therapeutic regimen; (2) medical condition; (3) lifestyle; (4) requests for services or medications; (5) psychosocial/feelings; (6) nonmedical/procedural; (7) asks for understanding; (8) asks for reassurance; (9) paraphrase/ checks for understanding; (10) bid for repetition; and (11) personal remarks/social conversation. Directly after the visit, patients completed the Newest Vital Sign (NVS) health literacy test, a sociodemographic survey (including age, sex, race, work status, marital status, insurance status), and three Patient-Reported Outcomes Measurement Information System-based questionnaires: Upper-Extremity Function, Pain Interference, and Depression. The NVS scores were divided into limited (0-3) and adequate (4-6) health literacy as done by the tool's creators. We also assessed whether the surgeons prompted patients to ask questions during the encounter. Results Patients with limited health literacy asked fewer questions than patients with adequate health literacy (5 ± 4 versus 9 ± 7; mean difference, À4; 95% CI, À7 to À1; p = 0.002). More specifically, patients with limited health literacy asked fewer questions regarding medical-care issues such as their therapeutic regimen (1 ± 2 versus 3 ± 4; Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. This work was performed at