RATIONALE: Neuroleptic malignant syndrome (NMS) is a rare, life-threatening complication of neuroleptic (antipsychotic) medications. Paliperidone is an atypical antipsychotic used in the treatment of schizophrenia. While current evidence suggests that atypical oral antipsychotics have a lower incidence of NMS compared to typical oral antipsychotics, there is limited information available on the incidence and management of NMS associated with long-acting injectable (LAI) antipsychotics. More case studies are needed to fully understand the true incidence of NMS associated with LAI atypical antipsychotics. This report aims to present our experience with a patient with schizophrenia who developed NMS as a result of taking LAI paliperidone, an atypical antipsychotic. PATIENT CONCERNS: A 63-year-old male diagnosed with schizophrenia was brought to the emergency room with complaints of high fever, muscle contraction, tremors, urinary and fecal incontinence, and a change of consciousness, which started 2 days after the first LAI paliperidone injection. During the psychiatric examination, the patient exhibited tremors, a high fever of 39.5°C, and muscle rigidity. He was confused and had impaired orientation. The patient's creatine kinase, white blood cell count, aspartate aminotransferase, and alanine aminotransferase levels were measured at 1895 U/L, 13750/mm3, 55 IU/L, and 45 IU/L, respectively. The electrocardiogram showed sinus tachycardia. DIAGNOSES: The patient's psychiatric examination, vital signs, and laboratory results were consistent with NMS. INTERVENTIONS: The patient received treatment with bromocriptine and amisulpride for 13 days. OUTCOMES: With this treatment, the patient's delirium improved and the patient became stable. The levels of creatine kinase, white blood cell count, aspartate aminotransferase, and alanine aminotransferase decreased to normal values. The patient was discharged from the hospital after 14 days of treatment. LESSONS: Although NMS is not very common in patients using antipsychotics, it is important because it is an emergency condition that can result in death if not treated appropriately. Clinicians should consider NMS in patients taking atypical antipsychotics such as paliperidone.