This descriptive observational study was conducted to increase understanding of medication administration practices during actual clinical use between 2 commonly used, different types of intravenous (IV) smart pumps. Compliance with manufacturer-recommended setup requirements for both primary and secondary infusions and secondary medication administration delay was compared between a head-height differential system and a cassette system. A total of 301 medication administration observations were included in this study: 102 (34%) for the linear peristaltic IV smart pump (medical–surgical: N = 51; critical care: N = 51) and 199 (66%) for the cassette pump (medical–surgical: N = 88; critical care: N = 111). Results found a 0% compliance for primary line setup and 84% compliance for secondary line setup and 1 omitted medication due to a closed clamp with the linear peristaltic system. For the cassette system, there are no head-height requirements. Two roller clamps were found to be in the closed position on initiation of the secondary infusion, but the clinician was alerted by an alarm, so no medication delays occurred. These findings support that the current system requirements for flow rate accuracy using head-height differential systems are difficult to achieve consistently at the point of care. There is a need for additional human factor designed technology to replace manual actions to improve the process of care for nurses and the safety of care for patients.