Background: There has been a shift towards the utilization of outpatient delivery of intensive chemotherapy due to potential improvements in quality of life measures and resource utilization. Herein, we aim to report the findings of a five-year quality improvement project comparing the outcomes and healthcare costs of outpatient and inpatient delivery of post-induction intensive chemotherapy amongst patients with hematological neoplasms. Methods: Using Plan-Do-Study-Act (PDSA) methodology, a multidisciplinary team was established to determine appropriate strategies for delivering outpatient intensive chemotherapy and improving healthcare resource utilization. Records of patients receiving inpatient chemotherapy from 2016-2017 were retrospectively reviewed. Process mapping was utilized to design interventions to facilitate the outpatient delivery of chemotherapy. The interventions included the initiation of an outpatient chemotherapy clinic, creating clinical pathways for chemotherapy protocols, developing educational materials for patients and healthcare staff, and facilitating access to emergency care services. During 2018-2022, patients were prospectively identified and enrolled to receive outpatient chemotherapy. Results: 288 patients were enrolled with 70 (24.3%) receiving inpatient chemotherapy and 218 (75.7%) receiving outpatient chemotherapy. The median age for the inpatient and outpatient chemotherapy groups was 34 and 38, respectively [P = 0.027]. Patients enrolled in this project had diagnoses of acute leukemia (53.2%), Hodgkin’s lymphoma 16.3%, and non-Hodgkin’s lymphoma (30.6%). Febrile neutropenia was observed in 64.3% of patients receiving inpatient chemotherapy and in 27.5% of patients receiving outpatient chemotherapy [P < 0.001]. Death during the course of the chemotherapy regimens was seen in 4% of patients receiving inpatient chemotherapy compared to 0.5% of outpatient chemotherapy patients [P = 0.003]. Outpatient chemotherapy resulted in a 53.4% reduction in total bed days occupied. The estimated total cost saving due to this intervention during the years of 2018-2022 was $2.88 million USD. Conclusions: Outpatient delivery of intensive chemotherapy for hematological malignancies is an effective approach which results in comparable safety outcomes and significant improvements in cost-effectiveness and resource utilization.