Sparse evidence exists about how short peripheral catheter (SPC) duration is affected by the presence of a saline lock versus continually infusing fluids. Often the choice to lock an SPC with saline is based on provider preference, rather than available evidence or patient-centered factors. This study compared the duration of 85 SPCs: locked with saline versus continuously running fluids. A secondary analysis considered the influence of a number of intermittent medications and flushes. Although the saline-locked group had a slightly longer duration time, it was not statistically significant. Factors such as desire to ambulate or nighttime saline flushes merit consideration in SPC care decisions and standardized nurse-driven protocols.