People with chronic epilepsy (PWE) often make costly, and clinically unnecessary emergency department (ED) visits. Some do it frequently. No studies have examined interventions to reduce them. An intervention delivered by an epilepsy nurse specialist (ENS) might reduce visits. The rationale is it may optimize patients' self-management skills and knowledge of appropriate ED use. We examined such an intervention's clinical- and cost-effectiveness. Eighty-five adults with epilepsy were recruited from three London EDs with similar catchment populations. Forty-one PWE recruited from two EDs received treatment-as-usual (TAU) and formed the comparison group. The remaining 44 PWE were recruited from the ED of a hospital that had implemented a new ENS service for PWE attending ED. These participants formed the intervention group. They were offered 2 one-to-one sessions with an ENS, plus TAU. Participants completed questionnaires on health service use and psychosocial well-being at baseline, 6- and 12-month follow-up. Covariates were identified and adjustments made. Sixty-nine (81%) participants were retained at follow-up. No significant effect of the intervention on ED visits at 12 months or on other outcomes was found. However, due to less time as inpatients, the average service cost for intervention participants over follow-up was less than for TAU participants' (adjusted difference £558, 95% CI, -£2409, £648). Covariates most predictive of subsequent ED visits were patients' baseline feelings of stigmatization due to epilepsy and low confidence in managing epilepsy. The intervention did not lead to a reduction in ED use, but did not cost more, partly because those receiving the intervention had shorter hospital admissions. Our findings on long-term ED predictors clarifies what causes ED use, and suggests that future interventions might focus more on patients' perceptions of stigma and on their confidence in managing epilepsy. If addressed, ED visits might be reduced and efficiency-savings generated. © 2014 Noble et al.