This study was designed to assess healthcare resource utilization (HCRU) and costs in patients with newly diagnosed schizophrenia based on timing and context of long-acting injectable antipsychotic agent (LAI) initiation. Using claims data, patients (aged 18–40 years) with first schizophrenia diagnosis January 2013–September 2019 (index date), no LAI or oral antipsychotic agent claims during 12-month preindex period, and continuous benefit enrollment from 12 months before index date to 12 months after first LAI administration were identified. Patients were grouped based on timing [early (≤1 year after index date) vs. late] and circumstances [reactive (after schizophrenia-related event) vs. proactive] of LAI initiation. Of 1290 patients with at least one LAI claim, 306 met criteria for early (n= 204; reactive,n= 107; proactive,n= 97) and late (n= 102;n= 75;n= 27) initiation. HCRU and costs were numerically lower in early versus late groups, and significantly lower for proactive initiation in both groups. Comparing worst-case (late-reactive) and best-case (early-proactive) scenarios, the average annual cost difference was $7195.13 (P= 0.0233), with major drivers being emergency department ($171.28;P< 0.05) and other outpatient ($2845.73;P< 0.00001) visits. In addition to the clinical advantages previously described in the literature, the proactive use of LAIs in early-phase schizophrenia is associated with lower healthcare costs.