As a first step in the development of a health-related quality of life (HRQOL) instrument, we conducted in-depth interviews to identify the specific concerns of adults with strabismus. Prospective cross-sectional study. Thirty adults with strabismus, 17 with diplopia, and 13 without were recruited. Individual interviews, using 11 open-ended questions, were audiotaped, transcribed, and transcripts reviewed independently by three investigators. Phrases regarding how strabismus affected everyday life were grouped into topic areas and the frequency of each topic analyzed for subjects with and without diplopia. A total of 1,508 phrases were extracted: 207 (14%) of 1,508 were excluded because they did not pertain to HRQOL. From the remaining 1,301 phrases, 48 topic areas were apparent. For patients with diplopia, the most frequently occurring topics were: nonspecific negative feeling (15/17; 88%) ("really hard"); general disability (15/17; 88%) ("affects everything"); and driving (14/17; 82%). In those without diplopia, the most frequently mentioned topics were appearance to others (12/13; 92%) ("people notice my eyes") followed by problems with eye contact (10/13; 77%) and interpersonal relationships (10/13; 77%). Of the topics that were common to both groups (n = 42), two of the most frequent were driving and nonspecific negative feeling. Multiple individual interviews revealed many topics that negatively affect quality of life in patients with strabismus. The frequency and type of concerns confirm the importance of HRQOL assessment as an important aspect of strabismus management.