Our objective was to measure direct (hospital and NHS) and indirect (patient/caregiver) costs of following up in-home compliance to non-invasive ventilation via wireless modem. We constructed a prospective controlled trial of 40 consecutive ALS home-ventilated patients, randomly assigned according to their residence area to G1 (nearby hospital, office-based follow-up) and G2 (outside hospital area, telemetry device-based follow-up). Total NHS direct cost encompassed costs related to outpatients' visits (office and emergency room) and hospitalizations. Hospital direct costs included transportation to/from hospital, office visit per hour cost and equipment maintenance. Non-medical costs considered days of wages lost due to absenteeism. G1 included 20 patients aged 60 ± 10 years and G2 included 19 patients aged 62 ± 13 years. Results showed that no differences were found regarding clinical/demographic characteristics at admission. NHS costs showed a 55% reduction in average total costs with a statistically significant decrease of 81% in annual costs per patient in G2. Hospital costs were found to be significantly higher in G2 with regard to total costs (64% average increase) but not annual costs (7%). No statistical difference was found with regard to expenses from absenteeism. In conclusion, at the cost of an initial financial constraint to the hospital per year (non-significant), telemonitoring is cost-effective, representing major cost savings to the NHS in the order of 700 euros/patient/year.