BACKGROUND: There has been increasing interest in the potential for pre-emptive interventions in the prodrome of autism, but little investigation as to their effect. METHODS: A two-site, two-arm assessor-blinded randomised controlled trial (RCT) of a 12-session parent-mediated social communication intervention delivered between 9 and 14 months of age (Intervention in the British Autism Study of Infant Siblings-Video Interaction for Promoting Positive Parenting), against no intervention. Fifty-four infants (28 intervention, 26 nonintervention) at familial risk of autism but not otherwise selected for developmental atypicality were assessed at 9-month baseline, 15-month treatment endpoint, and 27- and 39-month follow-up. PRIMARY OUTCOME: severity of autism prodromal symptoms, blind-rated on Autism Observation Schedule for Infants or Autism Diagnostic Observation Schedule 2nd Edition across the four assessment points. SECONDARY OUTCOMES: blind-rated parent-child interaction and child language; nonblind parent-rated communication and socialisation. Prespecified intention-to-treat analysis combined estimates from repeated measures within correlated regressions to estimate the overall effect of the infancy intervention over time. RESULTS: Effect estimates in favour of intervention on autism prodromal symptoms, maximal at 27 months, had confidence intervals (CIs) at each separate time point including the null, but showed a significant overall effect over the course of the intervention and follow-up period (effect size [ES] = 0.32; 95% CI 0.04, 0.60; p = .026). Effects on proximal intervention targets of parent nondirectiveness/synchrony (ES = 0.33; CI 0.04, 0.63; p = .013) and child attentiveness/communication initiation (ES = 0.36; 95% CI 0.04, 0.68; p = .015) showed similar results. There was no effect on categorical diagnostic outcome or formal language measures. CONCLUSIONS: Follow-up to 3 years of the first RCT of a very early social communication intervention for infants at familial risk of developing autism has shown a treatment effect, extending 24 months after intervention end, to reduce the overall severity of autism prodromal symptoms and enhance parent-child dyadic social communication over this period. We highlight the value of extended follow-up and repeat assessment for early intervention trials.