OBJECTIVE: To evaluate a prevention program for infant sleep and cry problems and postnatal depression. METHODS: Randomized controlled trial with 781 infants born at 32 weeks or later in 42 well-child centers, Melbourne, Australia. Follow-up occurred at infant age 4 and 6 months. The intervention including supplying information about normal infant sleep and cry patterns, settling techniques, medical causes of crying and parent self-care, delivered via booklet and DVD (at infant age 4 weeks), telephone consultation (8 weeks), and parent group (13 weeks) versus well-child care. Outcomes included caregiver-reported infant night sleep problem (primary outcome), infant daytime sleep, cry and feeding problems, crying and sleep duration, caregiver depression symptoms, attendance at night wakings, and formula changes. RESULTS: Infant outcomes were similar between groups. Relative to control caregivers, intervention caregivers at 6 months were less likely to score >9 on the Edinburgh Postnatal Depression Scale (7.9%, vs 12.9%, adjusted odds ratio [OR] 0.57, 95% confidence interval [CI] 0.34 to 0.94), spend >20 minutes attending infant wakings (41% vs 51%, adjusted OR 0.66, 95% CI 0.46 to 0.95), or change formula (13% vs 23%, P < .05). Infant frequent feeders (>11 feeds/24 hours) in the intervention group were less likely to have daytime sleep (OR 0.13, 95% CI 0.03 to 0.54) or cry problems (OR 0.27, 95% CI 0.08 to 0.86) at 4 months. CONCLUSIONS: An education program reduces postnatal depression symptoms, as well as sleep and cry problems in infants who are frequent feeders. The program may be best targeted to frequent feeders.