Use of peripherally inserted central catheters (PICCs) has grown substantially in recent years. Increasing use has led to the realization that PICCs are associated with important complications, including thrombosis and infection. Moreover, some PICCs may not be placed for clinically valid reasons. Defining appropriate indications for insertion, maintenance, and care of PICCs is thus important for patient safety. An international panel was convened that applied the RAND/UCLA Appropriateness Method to develop appropriate indications for PICC use across patient populations. These criteria can be used to improve care, inform quality improvement efforts, and advance the safety of medical patients.