<b>Background:</b> Inappropriate albumin use in clinical practice remains problematic. Health-systems face continued challenges in promoting cost-appropriate use. <b>Objective:</b> To evaluate the clinical and economic impact of a clinical pharmacist–led intervention strategy targeting inappropriate albumin use in general ward patients. <b>Methods:</b> A retrospective cohort study evaluated all adult (≥18 years) general ward patients administered ≥1 dose of albumin at a university medical center over a 2-year period. The intervention consisted of a clinical pharmacist–led strategy intervening on all albumin orders not in accordance with institutional guidelines. The primary end point was to compare inappropriate albumin utilization before and after implementation. Secondary end points compared the rates of inappropriate albumin use adjusted for hospital admission and patient-days as well as associated costs by appropriateness between study periods. <b>Results:</b> A total of 4420 patients were screened, with 1971 (44.6%) patients meeting inclusion criteria. The clinical pharmacist strategy significantly reduced inappropriate albumin (grams) utilization by 86.0% (<i>P</i> < 0.001). A 7-fold reduction of inappropriate albumin administered adjusted for the number of patient admissions was found from the preimplementation period following clinical pharmacist intervention strategy implementation (415.3 ± 83.2 vs 57.5 ± 34.2 g per 100 general ward hospital admissions, respectively; <i>P</i> < 0.001). Also, the adjusted inappropriate albumin rate was reduced from 62.2 ± 12.3 to 8.6 ± 5.2 g per 100 patient-days in the preimplementation and postimplementation periods, respectively (<i>P</i> < 0.001). Annual cost savings were $421 455 overall, with $341 930 resulting from mitigation of inappropriate use. <b>Conclusion and Relevance:</b> Clinical pharmacist–led interventions significantly reduced inappropriate albumin use and costs in hospitalized patients.