OBJECTIVES: Development of validated patient-reported outcome (PRO) measures has the potential to positively impact scientific research and patient management.  To date, the specific issues and symptoms most relevant to DM1 patients’ health related quality-of-life (HRQOL) have not been systematically assessed.  Our goal is to identify those aspects of HRQOL that are most important to patients with DM1, a neuromuscular condition with multisystemic organ dysfunction. METHODS: We conducted in-depth individual patient interviews with twenty genetically confirmed, adult, DM1 patients representing varied levels of disability.  Each interview focused on identifying the DM1 issues that have the greatest impact on patient HRQOL.  Each interview was recorded, transcribed, coded, and analyzed using a qualitative framework technique, triangulation, and three investigator consensus approach. RESULTS: A total of 1175 direct quotes were coded resulting in 223 like themes.  These themes were subsequently categorized into 7 subdomains representing physical, mental, and social aspects of DM1 HRQOL.  A disease-specific HRQOL conceptual model was created for DM1 representing the most relevant symptomatic and psychosocial issues in this population.   Categories in this model included: 1) mobility and ambulation/ fine motor and upper extremity dysfunction; 2) emotional distress; 3) cognitive impairment; 4) social role limitations; 5) social role dissatisfaction; 6) activity impairment; and, 7) DM1-specific symptoms of: sleep disturbance, fatigue, pain/myotonia, gastrointestinal dysfunction, central sensory impairment, and communication difficulties.  Difficulty with ambulation was the most frequently mentioned issue by our sample of patients.  CONCLUSIONS: There are multiple themes and symptoms, some previously underrecognized, that play a key role in DM1 patient reported HRQOL.  These issues must be carefully examined in order to develop a representative disease-specific conceptual model and PRO measurement tool.  The development of such an instrument has the potential to improve DM1 clinical care and maximize the impact and relevance of future DM1 clinical research.