Background: The need for peripheral intravenous (IV) access in anatomically challenging patients is becoming a more commonly encountered clinical problem. The significant investment devoted to physician training for ultrasound-guided vascular access has not yet been matched by a similar commitment to nursing. Nurses, paramedics, and physicians are becoming more enthusiastic about peripheral IV access with ultrasound (PIVUS); however, institutional and clinician support has not yet been forthcoming. The learning curve for PIVUS has never been rigorously studied, and may be flatter than previously assumed. Methods: Registered nurses were selected to participate as trainees. Training involved 1:1 sessions consisting of formal orientation to portable ultrasound, mentoring, and practice sessions with a nurse practitioner who has expertise in ultrasound-guided peripheral vascular access; hands-on, supervised practice cannulating vessels on a nonhuman tissue simulator; and supervised attempts on live patients. Results: Seven of 8 trainees completed the training. The average number of patient encounters required to achieve 10 successful IV placements was 25 (range ¼ 18-32). The average time required for successful vessel cannulation was 19.57 minutes (range ¼ 5-62 minutes). An average of 25 attempts was required to achieve proficiency, and average of 50 cases was required to maintain consistency. Conclusions: In today's practice environment, PIVUS skills are increasingly important. The results of our study demonstrate that, with appropriate hands-on training and supervision, these skills can be effectively taught to registered nurses.