Self-harm is a major challenge to public health. Emergency department (ED) nurses treat significant proportions of patients with self-harm injuries, and positive therapeutic patient–nurse interactions are imperative to the physical and psychological outcome of this vulnerable patient group. Research, both nationally and internationally, suggests that treating those with self-harm injuries is emotionally challenging, and ambivalence, powerlessness, and ineffectiveness are commonly manifested in negative attitudes towards these patients. Following the PRISMA guidelines, this systematic review with meta-analyses examined the attitudes of ED nurses towards patients who self-harm, based on currently available evidence. The following databases were searched: CINAHL complete; Medline complete; PsycARTICLES; PsycINFO; The Allied and Complementary Medicine Database; Health Source: Nursing/Academic Edition; PsycEXTRA; and Psychology and Behavioural Sciences Collection. Clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant reports to identify additional studies, were also searched. Five studies were included in the meta-analysis. The Self-Harm Antipathy Scale (SHAS) was used as an outcome in two studies appropriate for meta-analysis. The Attitudes Towards Deliberate Self-Harm Questionnaire (ADSHQ) scale was used as an outcome in three studies appropriate for meta-analysis. Results demonstrated limited empathy and negativity towards patients who self-harm, indicating a requirement for education and supervision of ED staff, where the SHAS or the ADSHQ can be used to monitor attitude change. Self-harm educational content for ED staff should include areas of knowledge building including explanations and causes of self-harm; range, forms, and functions of self-harm; staff responses to self-harm; assessment, management, and interventions; professional practice issues.