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Background: We investigated the effectiveness of Nurse‐Family Partnership (NFP), a prenatal‐to‐age‐two‐years home‐visiting programme, in British Columbia (BC), Canada. Methods: For this randomised controlled trial, we recruited participants from 26 public health settings who were: <25 years, nulliparous, <28 weeks gestation and experiencing socioeconomic disadvantage. We randomly allocated participants (one‐to‐one; computer‐generated) to intervention (NFP plus existing services) or comparison (existing services) groups. Prespecified outcomes were prenatal substance exposure (reported previously); child injuries (primary), language, cognition and mental health (problem behaviour) by age two years; and subsequent pregnancies by 24 months postpartum. Research interviewers were masked. We used intention‐to‐treat analyses. (ClinicalTrials.gov, NCT01672060.) Results: From 2013 to 2016 we enrolled 739 participants (368 NFP, 371 comparison) who had 737 children. Counts for child injury healthcare encounters [rate per 1,000 person‐years or RPY] were similar for NFP (223 [RPY 316.17]) and comparison (223 [RPY 305.43]; rate difference 10.74, 95% CI ‐46.96, 68.44; rate ratio 1.03, 95% CI 0.78, 1.38). Maternal‐reported language scores (mean, M [SD]) were statistically significantly higher for NFP (313.46 [195.96]) than comparison (282.77 [188.15]; mean difference [MD] 31.33, 95% CI 0.96, 61.71). Maternal‐reported problem‐behaviour scores (M [SD]) were statistically significantly lower for NFP (52.18 [9.19]) than comparison (54.42 [9.02]; MD ‐2.19, 95% CI −3.62, −0.75). Subsequent pregnancy counts were similar (NFP 115 [RPY 230.69] and comparison 117 [RPY 227.29]; rate difference 3.40, 95% CI ‐55.54, 62.34; hazard ratio 1.01, 95% CI 0.79, 1.29). We observed no unanticipated adverse events. Conclusions: NFP did not reduce child injuries or subsequent maternal pregnancies but did improve maternal‐reported child language and mental health (problem behaviour) at age two years. Follow‐up of long‐term outcomes is warranted given that further benefits may emerge across childhood and adolescence. [ABSTRACT FROM AUTHOR]