Few international studies have investigated factors affecting domiciliary non-invasive ventilation (D-NIV) compliance, and data from the UK are limited. We assessed compliance (defined as ≥ 4 h/night for at least 70% of the time) in a retrospective UK population study, at three time points (0–1 month, 3–4 months and 11–12 months), for all patients commenced on D-NIV over a 5-year period. A total of 359 patients were included. Non-compliant vs. compliant patients were significantly younger (median age 64 (IQR 52–72) vs. 67 (58–75) years, p = 0.032) and more likely to have schizophrenia, consistent at both 3–4 months (5% vs. 1%, p = 0.033) and 11–12 months (5% vs. 2%, p = 0.049). Repeated measures ANOVA demonstrated that the minutes [median (IQR)] of D-NIV used significantly increased at the three time points (0–1 month, 3–4 months and 11–12 months) for patients with hypertension [310 (147.5–431) vs. 341 (89–450) vs. 378 (224.5–477.5), p = 0.003]; diabetes [296.5 (132.5–417.5) vs. 342.5 (94.5–438.5) vs. 382 (247.5–476.25), p = 0.002] and heart failure [293 (177–403) vs. 326 (123–398) vs. 365 (212–493), p = 0.04]. In conclusion, younger and comorbid schizophrenic patients have lower D-NIV compliance rates, and our data suggest that persistence with D-NIV over a year may improve overall use.