Although mindfulness-based interventions (MBIs) have been established as evidence-based nonpharmacological treatments for chronic pain, there has been little systematic study of its potential risks, although concerns about harms have been raised. To address this gap, we examined differences in psychological and physical worsening among participants in the usual care and intervention conditions of a three-group, randomized pragmatic trial (Learning to Apply Mindfulness to Pain; LAMP) that tested the effectiveness of two approaches to delivering MBIs for chronic pain. The sample consisted of 368 male and 336 female veterans with chronic pain who completed a 10-week follow-up survey (86% response rate), 63% of whom had a mental health diagnosis. Psychological and physical worsening was assessed by a checklist asking participants if they experienced specific symptoms since beginning the study. Participants in usual care were more likely than those in the MBIs to report experiencing symptoms (53% versus 25%) including: disturbing memories (13% versus 6%); feeling more upset than usual when something reminded them of the past (16% versus 7%); feelings of sadness (19% versus 6%); feelings of anxiousness (27% versus 11%); feeling more tired or fatigued than usual (42% versus 14%); feeling more isolated or lonely (23% versus 8%); and a worsening of their physical or mental symptoms (13% versus 4%). We conclude that the LAMP MBIs did not cause harm and instead appeared to result in fewer side effects for this population of patients with chronic pain and high levels of mental health comorbidities. Funding: Department of Defense, W81XWH-18–2-0003. Department of Defense, W81XWH-18–2-0003.