<p>This study interpreted and translated a home visiting parenting program, <i>Promoting First Relationships</i>® (PFR), from English into Spanish and assessed if participants’ preferred language for PFR (Spanish, English) moderated its effect. This was a randomized controlled trial (PFR v. control) among 252 Spanish- and English-speaking mother-infant dyads (infant aged 6–12 weeks at enrollment) with low income who had previously received a mental health referral during their pregnancy. Outcomes were assessed at baseline, immediately post-intervention, and 6 months post-intervention. Outcomes included parenting sensitivity, dyadic synchrony, caregiver understanding of infant/toddler social-emotional needs (“caregiver understanding,” for brevity), maternal confidence, infant difficulty, and infant social-emotional development. Results showed that differences in outcomes by condition were similar across the preferred language groups, with the exception of caregiver understanding measured at 6 months post-intervention (<i>b</i> = 1.52, <i>SE</i> = 0.52). On this outcome, PFR demonstrated a greater effect among mothers who preferred Spanish (<i>d</i> = 0.69) than English (<i>d</i> = 0.40). Follow-up analyses of self-identified ethnicity (Hispanic or non-Hispanic) and nativity (non-US-born or US-born) as moderators showed similar results. There was no evidence that PFR worked differently across language, self-identified ethnicity, and nativity groups, with the exception of stronger PFR-related gains on caregiver understanding among mothers who preferred Spanish, self-identified as Hispanic, and were born outside the US.</p><p>Trial registration: ClinicalTrials.gov, NCT02724774, registered 3/31/2016</p>