Hospitals are subject to more economic pressures than ever before. On the one hand, cost containment or cost reduction is paramount, particularly in relation to costly branded pharmaceuticals. On the other hand, quality measures and value-based reimbursement penalizes poor patient care. Multimodal analgesia sits squarely in this quandary, since its very nature requires use of multiple drugs with their associated costs, though this approach has the potential to improve quality of care. We undertook a comprehensive review of the pharmacoeconomics of IV acetaminophen, a new drug useful as part of a multimodal analgesic approach. While this new branded drug adds to direct drug costs, there is clear potential for IV acetaminophen to reduce the incidence of opioid-related adverse events and, in so doing, result in net hospital savings. This review describes many clinical studies showing significant improvements in postoperative nausea and vomiting, excessive sedation and pruritus. In addition, we describe studies demonstrating faster recovery times in the post-anesthesia care unit, intensive care unit and total hospital length of stay. Lastly, we summarize many studies demonstrating the robust effect of IV acetaminophen on patient satisfaction. A holistic view of total hospital performance should be adopted when reviewing drugs rather than a silo mentality within the pharmacy. While IV acetaminophen adds to drug costs, the body of evidence indicates this drug has the potential to improve outcomes and hospital efficiency.