Objective: Compare the effect of seated Tai Chi exercise (intervention) to usual activities on quality of life and depression symptoms in older people using wheelchairs. Design: Randomized controlled trial. Setting: One long-term care facility in Taiwan. Participants: 86 long-term care residents were screened; 60 were eligible and randomized to Tai Chi group (n = 30), or usual activity (n = 30). Intervention: One certified trainer provided the intervention group with 40 min of seated Tai Chi exercise, three times a week for 26 weeks. Trial registration ACTRN12613000029796. Main outcome measures: Quality of Life (WHOQOL (BREF)); depression symptoms (GDS-SF) Results: Participants in the Tai Chi group (M = 3.76, SD = 3.65) recorded significantly lower GDS-SF scores than participants in the control (M = 7.76, SD = 5.15) and the Tai Chi group registered significantly higher scores across overall QOL [p = 0.03], general health [p = 0.04], and the associated domains: physical health [p = 0.00], psychological health [p = 0.02], social relations [p = 0.00], and environment [p = 0.00]. Conclusions: The findings highlight the importance of Tai Chi in improving QOL and depression in this population.