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Background Inappropriate packed red blood cell (pRBC) transfusions increase patient risk and healthcare costs. Initial audits at Niagara Health (Ontario, Canada) revealed only 85% and 54% compliance with Choosing Wisely Canada guidelines for pre-transfusion hemoglobin (≤80 g/L) and single-unit transfusion, respectively.Methods We conducted a nonrandomized, interrupted time-series Quality Improvement Project (QIP) using the Model for Improvement. Interventions included technologist-led prospective screening of pRBC orders, policy updates, and educational campaigns. Outcome measures were rates of inappropriate transfusions based on hemoglobin and single-unit criteria; balancing measures included transfusion-related adverse events. Sustainability was assessed using Statistical Process Control charts. Cost analysis estimated savings using an activity-based cost of $C1500 per pRBC unit.Results Initial implementation improved compliance to 90% (pre-transfusion hemoglobin) and 71% (single-unit) within three months. Extended analysis (2021–2024) demonstrated sustained rates of 90% and 77%, respectively. At the St. Catharines Site, monthly median transfusions decreased from 273 to 173 units, yielding a 56% reduction in RBC utilization and 44% cost savings amounting to $C5052000.Conclusions Technologist-led screening achieved sustained improvements in transfusion appropriateness, leading to substantial cost savings. Variability across sites underscores the need for further research on contextual factors influencing future QIP success.