Irritable bowel syndrome (IBS) is a common condition associated with recurrent abdominal pain and altered bowel habits. It is particularly pernicious to youth, who may withdraw from life tasks due to pain, diarrhea, and/or fear of symptoms. Emotional stress exacerbates IBS symptoms, and mind-body interventions may be beneficial. In this mixed-methods study of 18 teens aged 14 to 17 years undertaking a 6-week Iyengar yoga intervention, we aimed to identify treatment responders and to explore differences between responders and nonresponders on a range of quantitative outcomes and qualitative themes related to yoga impact, goodness of fit, and barriers to treatment. Half of the teens responded successfully to yoga, defined as a clinically meaningful reduction in abdominal pain. Responders differed from nonresponders on postintervention quantitative outcomes, including reduced abdominal pain, improved sleep, and increased visceral sensitivity. Qualitative outcomes revealed that responders reported generalized benefits early in treatment and that their parents were supportive and committed to the intervention. Responders and nonresponders alike noted the importance of home practice to achieve maximal, sustained benefits. This study reveals the need for developmentally sensitive yoga programs that increase accessibility of yoga for all patients.