Abstract Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative motor neuron disease that is rarely encountered in the obstetric population. This report describes the successful use of long-term mechanical ventilation in a pregnant woman with ALS. Case presentation: A 37-year-old G3P2 woman with ALS was admitted to the emergency room with shortness of breath, tachypnea, and evidence of hypoxic and hypercapnic respiratory failure at 24 weeks of gestation, precipitated by bacterial pneumonia. Antibiotic therapy, intubation, and mechanical ventilatory support were initiated, followed by an early tracheostomy as soon as the need for prolonged airway access was identified. The mother remained with prolonged mechanical ventilation until spontaneous preterm birth occurred at 32 weeks of gestation, with the vaginal delivery of a healthy infant. The mother was discharged from the intensive care unit during puerperium to continue mechanical ventilation support in a home care facility. Conclusion: Long-term mechanical ventilation can be successfully performed during pregnancy. Goals of oxygenation and ventilation need to be modified and customized based on the underlying condition and the status of the mother.