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Most interventions to prevent postpartum depression (PPD) focus on the mother rather than the mother–infant dyad. As strong relationships between infant sleep and cry behavior and maternal postpartum mood have been demonstrated by previous research, interventions targeted at the dyad may reduce symptoms of PPD. The goal of the current study was to examine the effectiveness of Practical Resources for Effective Postpartum Parenting (PREPP). PREPP is a new PPD prevention protocol that aims to treat women at risk for PPD by promoting maternally mediated behavioral changes in their infants, while also including mother-focused skills. Results of this randomized control trial (RCT) (n = 54) indicate that this novel, brief intervention was well tolerated and effective in reducing maternal symptoms of anxiety and depression, particularly at 6 weeks postpartum. Additionally, this study found that infants …