Background: Insomnia, a prevalent and troublesome side effect experienced by cancer survivors, significantly impairs recovery and survival. We conducted a nationwide, multicenter, phase III, blinded, randomized controlled trial testing whether 1) yoga is superior to survivorship health education (SHE) and 2) yoga is non-inferior to cognitive behavioral therapy for insomnia (CBT-I) for treating insomnia in survivors. Methods: The trial was conducted via the University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) Research Base. Participants were cancer survivors between 2-60 months post adjuvant therapy, with insomnia, no metastatic disease, and no yoga participation during the previous 3 months. Survivors were randomized into 1) YOCAS yoga (2x/wk; 75 min/sess for 4 wks with pranayama, asana, and dhyana, N = 251), 2) CBT-I (1x/wk, 90 min/sess for 8 wks with sleep hygiene, stimulus control, sleep restriction, and cognitive therapy, N = 238), or 3) SHE (2x/wk; 75 min/sess for 4 wks with ASCO-recommended survivorship education, N = 251). Insomnia was assessed pre- and post-intervention via the Insomnia Severity Index. Results: 740 eligible cancer survivors were enrolled (93% female, mean age = 56 + 11, 75% breast cancer). ANCOVAs with baseline values as covariates revealed YOCAS is significantly better than SHE for treating insomnia at post-intervention (CS = change score; CS mean diff = -1.43, SE = 0.42, p < 0.01). Yoga participants demonstrated greater improvements in insomnia from pre- to post-intervention (CS = -3.61, SE = 0.30) compared to SHE participants (CS = -2.19, SE = 0.33, all p < 0.01). Intent-to-treat analyses of non-inferiority (non-inferiority margin set at 1.15 a priori) showed YOCAS is inferior to CBT-I (CS mean diff = 3.52, CI = 2.55 - 4.50, p < 0.01). However, analyses of non-inferiority using the optimal treatment effect in fully compliant survivors were inconclusive regarding whether YOCAS is non-inferior to CBT-I for treating insomnia (CS mean diff = 2.20, CI = 0.42 - 3.98, p = 0.09). Significantly more survivors withdrew from CBT-I and SHE due, in part, to disliking the interventions compared to YOCAS (30%, 25%, and 16%, respectively, p < 0.01). Conclusions: YOCAS yoga is better than SHE and results are inconclusive as to whether yoga is non-inferior to CBT-I for treating insomnia among survivors. Clinicians should consider prescribing YOCAS and CBT-I for survivors reporting insomnia. Funding: NCI UG1CA189961, R01CA181064, T32CA102618. Clinical trial information: NCT02613364.