Background: Peripherally inserted central catheters (PICCs) have been used for years in Taiwan, but their broad usage has been restricted by their short durability and complications. Objective: The aim of this study was to evaluate the most important factors causing failure of PICCs by comparing 2 periods of retrospectively studied cases before and after we implemented nursing care improvements. Methods: We analyzed possible factors affecting the length of the insertion period, according to the reasons for catheter withdrawal after insertion, self-care ability, coagulation status, and other factors. We reviewed 2 different periods of PICC insertions at our hospital (133 and 143 cases, respectively) before and after an announcement of nursing educational comprehensive guidelines for post-PICC care. Results: In the first period, the most common complication due to PICC placement was wound oozing (24.7%), followed by infection/phlebitis (9.7 %), occlusion (6.7%), and leaking (3.8%). In the second period, comprehensive educational guidelines for post-PICC manipulation were provided. The outcomes of PICC insertions significantly improved from 33.8% in the first period to 64.3% in the second period (odds ratio, 3.53), and the complication rates of persistent oozing (7%), infection (4.2%), and occlusion (2.8%) significantly decreased. Conclusions: Changes in nursing care provided in the period 2 contributed to improvements in the success rate of PICC. Implications for Practice: This is the first study suggesting that cancer nursing practice for PICC could benefit from professional guidelines that reinforce in-service education, strict control of PICC candidates without risk of coagulopathies, and a special nursing care system for patients with poor self-care ability.