For an intervention delivered in early childhood to have meaningful translational effect, long-term follow-up is necessary, especially among underserved indigenous children among whom preventable dental disease is common. To test the long-term effectiveness of an early-childhood dental intervention through a follow-up at age 5 years among Aboriginal children in Australia. This secondary analysis of a randomized clinical trial followed up on participants of the Baby Teeth Talk Study, a 2-group parallel, outcome assessor-blinded, randomized clinical trial conducted among Aboriginal children in South Australia, Australia. Participants included 448 mother or caregiver-child dyads who were enrolled in the Baby Teeth Talk trial between February 2010 and May 2011 and were randomized in the present trial to the immediate intervention group or the delayed intervention group. Intention-to-treat principles were used for all data analyses to estimate the effect of the intervention on dental caries experience. Data analysis was performed from April 10 to May 27, 2019. The intervention comprised 4 services to participants: (1) dental care to mothers during pregnancy, (2) application of fluoride varnish to children's teeth, (3) anticipatory guidance in the form of oral health educational packages, and (4) motivational interviewing for pregnant mothers and children at ages 6, 12, and 18 months in the immediate intervention group and at ages 24, 30, and 36 months in the delayed intervention group. The primary outcome was the mean number, in the primary dentition, of decayed, missing, or filled teeth (dmft) at age 5 years. Individual components of the dmft index were examined, as was the prevalence of dmft greater than 0. Of the 449 Aboriginal mothers and children recruited, 223 (49.7%) were randomized to the immediate intervention group and 225 (50.1%) to the delayed intervention group. The mean dmft at age 5 years was 2.10 (95% CI, 2.04 to 2.16) for children in the immediate intervention group and 2.91 (95% CI, 2.83 to 3.00) for children in the delayed intervention group (adjusted mean difference, -1.02; 95% CI, -1.81 to -0.22). When considering children in nonmetropolitan locations, the differences were stark; the mean dmft was 2.46 (95% CI, 2.38-2.54) for children in the immediate intervention group and 3.65 (95% CI, 3.53 to 3.78) for children in the delayed intervention group, with an adjusted mean difference of -1.52 (95% CI, -2.61 to -0.43). Most of this difference was accounted for by missing teeth, with the mean number of missing teeth of children in the immediate intervention group living in nonmetropolitan locations being 0.29 (95% CI, 0.27 to 0.31) compared with 1.02 (95% CI, 0.96 to 1.07) for their counterparts in the delayed intervention group. A 3-fold difference was observed in the percentage of missing teeth greater than 0 between children in the immediate intervention group and those in the delayed intervention group (10.8 [95% CI, 10.2 to 11.4] vs 31.0 [95% CI, 30.1 to 31.8]). This trial found that a multifaceted initiative to reduce early-childhood caries continued to be efficacious in participating indigenous children aged 5 years, especially those residing in nonmetropolitan locations and with teeth missing because of dental disease. anzctr.org.au Identifier: ACTRN12611000111976.