Abstract Mindfulness meditation, a slow breathing practice that is predicated on cultivating nonreactive awareness, also reduces pain. The existing literature has been mixed in demonstrating whether mindfulness meditation is more effective than slow breathing alone (ie, sham-mindfulness meditation) at reducing pain. Furthermore, smaller sample sizes in prior work have hindered a clear understanding of how respiration rate and state anxiety contribute to analgesia during meditation. This study pooled data from 5 randomized controlled trials using paralleling interventions and methodologies in 245 healthy, pain-free, meditation-naïve individuals. Noxious heat (49°C; right calf) was used to test whether changes in respiration and state anxiety mediate the effects of (1) mindfulness meditation (n = 113), (2) a slow-breathing sham-mindfulness meditation technique (n = 73), and (3) a book-listening control (n = 60) on pain intensity ratings (“0” no pain; “10” worst pain imaginable). Three separate 3 (group) × 2 (pre- vs postmanipulation) repeated-measures analysis of variances assessed whether mindfulness and sham-mindfulness meditation significantly reduced pain, anxiety, and respiration, respectively. Mediation analyses examined whether changes in state anxiety and respiration, respectively, mediated analgesia during meditation. Mindfulness meditation produced significantly greater analgesia when compared with sham-mindfulness meditation and controls. Slower respiration rate partially mediated analgesia for mindfulness and sham-mindfulness meditation as compared with controls. Both meditation techniques significantly lowered anxiety, but these improvements did not mediate pain relief. The present findings demonstrate that mindfulness meditation is more effective than slow-breathing (sham-mindfulness) meditation at reducing pain and highlight the role of slower breathing in the direct modulation of acutely evoked pain by meditation.