Background/Objectives:The available evidence from randomised controlled trials suggests that vitamin B12 supplementation does not improve neurologic function in older people with marginal but not deficient Vitamin B12 status. This secondary analysis used data from the Older People and Enhanced Neurological function (OPEN) randomised controlled trial to assess whether baseline vitamin B12 status or change in vitamin B12 status over 12 months altered the effectiveness of dietary vitamin B12 supplementation on neurologic function in asymptomatic older people with depleted vitamin B12 status at study entry.Subjects/Methods:Vitamin B12 status was measured as serum concentrations of vitamin B12, holotranscobalamin, homocysteine and via a composite indicator (cB12). Neurological function outcomes included eleven electrophysiological measures of sensory and motor components of peripheral and central nerve function. Linear regression analyses were restricted to participants randomised into the intervention arm of the OPEN trial (n=91).Results:Analyses revealed an inconsistent pattern of moderate associations between some measures of baseline vitamin B12 status and some neurological responses to supplementation. The directions of effect varied and heterogeneity in effect across outcomes could not be explained according to type of neurological outcome. There was no evidence of differences in the neurological response to vitamin B12 supplementation according to change from baseline over 12 months in any indicator of B12 status.Conclusions:This secondary analysis of high-quality data from the OPEN trial provides no evidence that baseline (or change from baseline) vitamin B12 status modifies the effect of vitamin B12 supplementation on peripheral or central nerve conduction among older people with marginal vitamin B12 status. There is currently insufficient evidence of efficacy for neurological function to support population-wide recommendations for vitamin B12 supplementation in healthy asymptomatic older people with marginal vitamin B12 status.