The effectiveness of Promoting First Relationships (PFR), a 10-week home visiting program with video feedback, was tested in a randomized controlled trial involving 252 mothers and their 8- to 12-week-old infants. Mothers were eligible if they initiated treatment after mental health screening (depression, anxiety, posttraumatic stress disorder [PTSD]) at a community or public health primary care center in pregnancy. At baseline, 51% had mild to severe depression symptoms, 54% had mild to severe anxiety, and 35% had PTSD. Their ages ranged from 18 to 42 years. Mothers were 66% White, 18% Black, and 16% other races. Forty-seven percent identified as Hispanic, and 33% preferred to read and speak in Spanish. The median family annual income was less than $20,000. The PFR program or receipt of a resource packet (control condition) followed the baseline assessment and randomization; we assessed outcomes when infants were age 6 and 12 months. Compared to mothers in the control condition, mothers in the PFR condition had significantly (ps < 0.05) higher observed sensitivity scores at both follow-up time points (d = 0.25, d = 0.26), had improved understanding of infant-toddler social-emotional needs at both time points (d = 0.21, d = 0.45), and reported less infant externalizing behavior at age 12 months (d = 0.28). This study is the fourth completed randomized controlled trial of the PFR program, all involving populations experiencing adversity.