Rationale Deliberate self-poisoning (DSP), the most common form of deliberate self-harm, is closely associated with suicide. Identifying risk factors of DSP is necessary for implementing prevention strategies. Objectives This study aimed to evaluate the relationship between benzodiazepine (BZD) treatment in psychiatric outpatients and DSP cases at emergency departments (EDs). Methods We performed a retrospective nested case–control study of psychiatric patients receiving BZD therapy to evaluate the relationship between BZD use and the diagnosis of DSP at EDs using data from the nationwide Taiwan National Health Insurance Research Database. Results Regression analysis yielded an odds ratio (OR) and 95 % confidence interval (95 % CI) indicating that the use of BZDs in psychiatric outpatients was significantly associated with DSP cases at EDs (OR = 4.46, 95 % CI = 3.59–5.53). Having a history of DSP, sleep disorders, anxiety disorders, schizophrenia, depression, or bipolar disorder was associated with a DSP diagnosis at EDs (OR = 13.27, 95 % CI = 8.28–21.29; OR = 5.04, 95 % CI = 4.25–5.98; OR = 3.95, 95 % CI = 3.32–4.70; OR = 7.80, 95 % CI = 5.28–11.52; OR = 15.20, 95 % CI = 12.22–18.91; and OR = 18.48, 95 % CI = 10.13–33.7, respectively). After adjusting for potential confounders, BZD use remained significantly associated with a subsequent DSP diagnosis (adjusted OR = 2.47, 95 % CI = 1.93–3.17). Patients taking higher average cumulative BZD doses were at greater risk of DSP. Conclusion Vigilant evaluation of the psychiatric status of patients prescribed with BZD therapy is critical for the prevention of DSP events at EDs.