OBJECTIVES: To develop and validate a self-administered questionnaire assessing subjects' perception and experience with injection, and their acceptance of injection site reactions (ISR) including pain following influenza vaccination. METHODS: Following a literature review, the VAPI questionnaire was simultaneously developed in US English, German and French, based on interviews of subjects (n=33) vaccinated intramuscularly (IM) or intradermally (ID) with an influenza vaccine. Items were generated from subjects' verbatim, comprehension tested with elderly and adult vaccinees (n=23); then a linguistic validation was done. The initial, 44 item-version of the questionnaire was administered 21 days after vaccination to subjects from Belgium, France, Spain, the United Kingdom, Germany and Italy who were participating in clinical trials comparing ID versus IM influenza vaccination.Scale construction and item reduction were conducted using principal component and multitrait analyses with 549 English subjects. Psychometric validation of the final questionnaire was performed per country (n=5,543) and included: 1) construct validity by item convergent and discriminant validity, 2) internal consistency reliability by Cronbach's alpha and 3) clinical validity by describing the scores according to ISR severity. RESULTS: After item reduction, the final questionnaire comprised 4 multi-item dimensions (“bother”; “arm movement”; “sleep”; “acceptability”) grouping 16 items plus 5 individual items (anxiety before vaccination; bother by pain during vaccination; satisfaction with the injection system; anxiety of being vaccinated next year; willingness to be vaccinated again). Item convergent and discriminant validity was confirmed for all scales in most countries. Multi-item dimension internal consistency reliability was good to excellent for all countries (Cronbach's alpha ranging from 0.73 to 0.94), except for the “sleep” dimension in Italy (0.68). Dimension scores demonstrated good clinical validity: greater severity of ISR was associated with higher scores. CONCLUSION: The self-administered VAPI questionnaire is valid and reliable. Therefore, it is a promising tool for the assessment of the acceptance of a vaccine injection system.