OBJECTIVES: The aim of this study was to test the efficacy of a Mindfulness-Based Childbirth and Parenting Program (MBCP) in reducing pregnant women's perceived stress and preventing perinatal depression compared to an active control condition. METHOD: First time pregnant women (n = 197) at risk of perinatal depression were randomized to MBCP or an active control treatment, which consisted of a Lamaze childbirth class. At baseline and post-intervention, participants filled out questionnaires on perceived stress, depressive symptoms, positive states of mind, and five facets of mindfulness. RESULTS: Compared to the active control treatment, MBCP significantly reduced perceived stress (p = 0.038, d = 0.30) and depressive symptoms (p = 0.004, d = 0.42), and increased positive states of mind (p = 0.005, d = 0.41) and self-reported mindfulness (p = 0.039, d = 0.30). Moreover, change in mindfulness possibly mediated the treatment effects of MBCP on stress, depression symptoms, and positive states of mind. The subscales "non-reactivity to inner experience" and "non-judging of experience" seemed to have the strongest mediating effects. LIMITATIONS: The outcomes were self-report questionnaires, the participants were not blinded to treatment condition and the condition was confounded by number of sessions. CONCLUSIONS: Our results suggest that MBCP is more effective in decreasing perceived stress and risk of perinatal depression compared to a Lamaze childbirth class. The results also contribute to our understanding of the underlying psychological mechanisms through which the reduction of stress and depression symptoms may operate. Thus, this study increases our knowledge about efficient intervention strategies to prevent perinatal depression and promote mental wellbeing among pregnant women.