Background and objective: When home non-invasive ventilation (NIV) is initiated, five goals need to be achieved: a daily use >4 h/day, an improvement in gas exchange, health-related quality of life (HRQL) and sleep quality without side effects. Our aim was to assess how frequently these five goals were reached and the factors predictive of achievement. Methods: We conducted a monocentric cohort study that included patients electively established on home NIV over 2 years. HRQL was assessed at baseline and follow-up by the Severe Respiratory Insufficiency questionnaire. Adequate initiation was defined as the achievement of at least three of five goals and successful initiation as the achievement of all. Results: Two-hundred and fifty patients were included at baseline. NIV was initiated for: obesity hypoventilation syndrome (n = 95; 38%), neuromuscular disease (n = 70; 28%), chronic obstructive pulmonary disease (n = 66; 26%) and chest wall disease (n = 19; 8%). At follow-up, measures of all five goals were available in 141 (56%) patients. NIV initiation was adequate for 96 (68%) patients and successful for 12 (9%) patients. In multivariate analysis, a tidal volume ≥ 7.8 ml/kg of ideal body weight was associated with an increased likelihood of adequate NIV initiation (hazard ratio: 5.765 [95% CI:1.824–18.223], p = 0.006]. Improvement in daytime partial arterial carbon dioxide pressure (PaCO2) was not correlated to improvement in HRQL or sleep quality. Severe to very severe NIV-related side effects occurred in 114 (47%) patients and were associated with higher daytime PaCO2 (6.35 ± 1.08 vs. 5.92 ± 0.79 kPa, p < 0.001). Conclusion: Successful home NIV initiation is rarely achieved in real life. HRQL and NIV tolerance should be assessed to improve patient-centred outcomes.