Background: Clonazepam is a benzodiazepine drug indicated in all clinical forms of epileptic seizures, various forms of myoclonic seizures, myoclonus and other abnormal movements. At present, it is classified as a hazardous drug for workers, according to a technical document produced by the Spanish National Institute for Safety and Health at Work (INSST), in collaboration with the Spanish Society of Hospital Pharmacy (SEFH). Objectives: Administration of clonazepam in pre-filled syringes connected to a closed safety system, made in the pharmacy service, may facilitate its administration and reduce the risks to the health or safety of nursing personnel. Therefore, a physicochemical stability study of clonazepam in ready-to-use pre-filled syringes for oral and parenteral administration was carried out. Methods: A rapid, linear, precise and sensitive high-performance liquid chromatography (HPLC) method for chemical stability studies of Clonazepam 1 mg/mL (parenteral use) and 2.5 mg/mL (oral use) in solution was implemented after repackaging in pre-filled syringes. The studies were conducted by measuring concentrations of oral and parenteral Clonazepam in pre-filled syringes, at various time points, over 30 days in several different storage conditions: oral clonazepam protected from light in refrigerator and at controlled room temperature exposed to ambient light; parenteral clonazepam protected from light in refrigerator and at controlled room temperature protected or unprotected from light. Visual aspects and pH change as well as crystal formation were checked to determine physical stability. Results: The loss of the active ingredient in all groups was less than 10% after 30 days. No evidence of crystal formation, pH and visual aspect changes were observed. Conclusions: Clonazepam 1 mg/mL parenteral solution and 2.5 mg/mL oral solution in pre-filled syringes are stable for up to 30 days in the tested conditions. The centralized repackaging of clonazepam in pre-filled syringes, connected to a closed safety system, in the pharmacy service, reduces drug manipulation by nursing staff decreasing the risk of occupational exposure.