Rationale: Home mechanical ventilation (HMV) is an advanced medical therapy offered to children with medical complexity. Despite the growing pediatric HMV population in North America, there are limited studies describing healthcare use and predictors of highest costs using robust health administrative data. Objectives: To describe patterns of healthcare use and costs in children receiving HMV over a 14-year period in Ontario, Canada. Methods: We conducted a retrospective population-based cohort study (April 1, 2003, to March 31, 2017) of children aged 0-18 years receiving HMV via invasive mechanical ventilation or noninvasive ventilation. Paired t tests compared healthcare system use and costs 2 years before and 2 years after HMV approval. We developed linear models to analyze variables associated with children in the top quartile of health service use and costs. Results: We identified 835 children receiving HMV. In the 2 years after HMV approval compared with the 2 years prior, children had decreased hospitalization days (median, 9 [interquartile range, 3-30] vs. 29 [6-99]; P < 0.0001) and intensive care unit admission days (6.6 [1.9-18.0] vs. 17.1 [3.3-70.9]; P < 0.0001) but had increased homecare service approvals (195 [24-522] vs. 40 [12-225]; P < 0.0001) and outpatient pulmonology visits (3 [1-4] vs. 2 [1-3]; P < 0.0001). Total healthcare costs were higher in the 2 years after HMV approval (mean, CAD$164,892 [standard deviation, CAD$214,187] vs. CAD$128,941 [CAD$194,199]; P < 0.0001). However, all-cause hospital admission costs were reduced (CAD$66,546 [CAD$142,401] vs. CAD$81,578 [CAD$164,672]; P < 0.0001). The highest total 2-year costs were associated with invasive mechanical ventilation (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.24-5.31; reference noninvasive ventilation), number of medical devices at home (OR, 1.63; 95% CI, 1.35-1.96; reference no technology), and increased healthcare costs in the year before HMV initiation (OR, 2.23; 95% CI, 1.84-2.69). Conclusions: Children progressing to the need for HMV represent a worsening in their respiratory status that will undoubtedly increase healthcare use and costs. We found that the initiation of HMV in these children can reduce inpatient healthcare use and costs but can still increase overall healthcare expenditures, especially in the outpatient setting.