OBJECTIVES: The objective was to develop the Self-Injection Assessment Questionnaire© (SIAQ© Version 1) as a comprehensive instrument for use across diseases to assess the perceived advantages of self-injection (SI) and the potential limitations of SI — specifically, psychological, social or physical limitations. METHODS: The SIAQ© was developed following four steps: 1) in-depth face-to-face interviews involving focus groups with rheumatoid arthritis or Crohn's disease (two conditions characterised by different symptoms and physical limitations); 2) qualitative analysis and development of a conceptual model to illustrate the domains relevant to patients; 3) questionnaire item generation in US English using patients' verbatim; and 4) cognitive debriefing interviews to evaluate content validity. RESULTS: Perceived advantages of SI were: convenient treatment scheduling, feeling in control of the disease, few side-effects and high efficacy of the medication. In addition, some patients expressed psychological limitations (fear of needles, fear of pain, fear of self-injecting, lack of self-confidence in performing injections properly), physical limitations (device handling problems), social limitations (embarrassed ‘to use needles'), and storage problems. Thirty-three items were generated and tested during cognitive debriefing interviews. The final questionnaire (SIAQ© Version 1) is composed of 23 items grouped into six domains, which assess psychological limitations about injections in general; psychosocial limitations about SI in particular; physical limitations about pain and skin reactions; physical limitations about the usability of the SI device; convenience and satisfaction with SI; and willingness to continue SI. CONCLUSION: The SIAQ© can be used to assess the perceived advantages of SI (convenience and satisfaction) and the potential limitations of SI — specifically, psychological (fear of injections), social (acceptability) or physical aspects (usability and injection-site reactions such as pain) and willingness to continue SI in the future. The psychometric properties of the SIAQ© will be evaluated in clinical studies.