Objective: To evaluate the effects of a postnatal home-visiting programme delivered by community health nurses to socially disadvantaged mothers in South Australia. Design: The intervention group of 428 mothers lived in metropolitan Adelaide and the comparison group of 239 mothers lived in regional towns where the programme was not yet available. All participating mothers met health service eligibility criteria for enrolment in the home-visiting programme. Participants in both groups were assessed at baseline (mean child age=14.4 weeks SD=2.3), prior to programme enrolment, and again when the children were aged 9, 18 and 24 months. Setting: State-wide community child health service. Participants: 667 socially disadvantaged mothers enrolled consecutively. 487 mothers (73%) completed the 24-month assessment. Intervention: Two-year postnatal home-visiting programme based on the Family Partnership Model. Primary outcome measures: Parent Stress Index (PSI), Kessler Psychological Distress Scale and the Ages and Stages Questionnaire. Results: Mixed models adjusting for baseline differences were used to compare outcomes in the two groups. The mothers in the home-visiting group reported greater improvement on the PSI subscales assessing a mother's perceptions on the quality of their relationship with their child (1.10, 95% CI 0.06 to 2.14) and satisfaction with their role as parents (0.46, 95% CI -0.15 to 1.07) than mothers in the comparison group. With the exception of childhood sleeping problems, there were no other significant differences in the outcomes across the two groups. Conclusions: The findings suggest that home-visiting programmes delivered by community health nurses as part of routine clinical practice have the potential to improve maternal-child relationships and help mothers adjust to their role as parents. Clinical Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12608000275369.