Background and Objectives <p>While there has been an increase in Duchenne muscular dystrophy (DMD) clinical trials over the last couple of decades, there is still no cure. Many individuals with DMD spend much of their lives participating in clinical trials. The impact of clinical trial participation on quality of life (QoL) is not well understood. This study aimed to understand the aspects of clinical trial participation that impact QoL for families affected by DMD.</p> Methods <p>Qualitative interviews were conducted with patients aged ≥ 12 years and caregivers using a semi-structured interview guide. Participants described the clinical trial factors that impacted QoL and rated the impact of each factor using a 7-point Likert scale. Transcripts were single coded for themes. A Participant-Specific Total Impact Factor (PSTIF) score was derived using the mean score across factors identified as impacting QoL. Agreement was calculated using Cohen’s Kappa between PSTIF score and the participant’s reported net trial experience (positive, neutral, or negative).</p> Results <p>A total of 24 caregivers and 7 patients participated. Participants mentioned 23 clinical trial factors with an impact on QoL. While most participants (82%) had a negative PSTIF score, the majority (65%) described a positive overall experience with clinical trials. There was poor agreement (Kappa = 0.12) between PSTIF score and net clinical trial experience.</p> Conclusion <p>When patients and caregivers quantified the impact of specific clinical trial factors on QoL, the impact was primarily negative; however, the majority of participants described their overall trial experience as positive. The study’s findings have implications for the collection and interpretation of QoL data in interventional studies.</p>