Background: Amyotrophic Lateral Sclerosis (ALS) patients? initiation to Noninvasive-ventilation (NIV) in outpatient/telemedicine is a recent strategy due to pandemic challenges. However, it can be puzzling both for patients and health care providers. Aims:To prospectively consecutively enrol all ALS patients requiring NIV initiation in outpatients/telemedicine setting and to follow them via S3NIV questionnaire. Methods: All information of respiratory-function and muscular-strength tests and NIV details, S3NIV questionnaire, tracheotomy events, and deaths were prospectively collected in all consecutive patients admitted to our Ventilation out-patients clinic (Ventil-lab). Results: From July 2021 to December 2022 forty ALS patients were enrolled in our venti-lab via outpatients/telemedicine (35/5) setting. Male/Female % ratio was 52/48, spinal onset was present in 52% of patients, mean age 65±12 yo, mean Vital Capacity was 65±13 , mean peak cough flow 205±93, mean Snip 47±23 l/min. All patients were followed-up for a mean of 359±195 days, mean S3NIV score was 6.3. Six/40 (15%) patients died during follow up, 3/40 (7,5%)patients underwent tracheotomy and 3/40 patients are awaiting home ventilator delivery.Conclusions: This study demonstrated that outpatients/telemedicine NIV initiation in patients with ALS is feasible, reliable and successful. This study?s S3NIV results shows good ventilator adaptation and complicance, and they are consistent with preliminary S3Niv questionnaire validation results in neuromuscular category of patients. Further studies with larger number of patients will be needed to further reinforce these outcomes.