Canalization of vascular accesses is one of the most used techniques in hospitalization units. When talking about peripherally inserted catheters, we can differentiate between peripheral intravenous catheters (PIVC), midline catheters, and long peripheral catheters (LPC). Midline catheters are rarely used despite being recommended for intravenous therapies lasting more than six days. This research is a pilot study of a longitudinal clinical trial. It aims to compare the complications associated with intravenous therapy between the control group (CG) with a PIVC and the experimental group (EG) with a midline in an Internal Medicine Unit of a Spanish hospital for three months. In this study, 44 subjects participated, 25 in the CG and 19 in the EG. The duration of cannulation was longer in the experimental group (8.13 days vs. 3.22, p < 0.001), and the appearance of phlebitis was more significant in the control group (19 patients in CG and 25 patients in EG). Midlines have presented a longer duration of cannulation and fewer complications than the PIVC. This protocol was registered with ClinicalTrials.gov (NCT05512117).