Background: Home parenteral nutrition (HPN) has become a common therapy. There is still controversy regarding the possibility that peripherally inserted central catheters (PICCs) may diminish catheter-related blood stream infection (CRBSI) rates. Methods: We searched the PubMed database for studies reporting the rates of CRBSI with HPN. Study selection was performed independently by three investigators. Disagreements were discussed and resolved by consensus or by arbitration by an author not involved in the search. The National Institutes of Health Quality Assessment Tools was used to assess the methodological quality of the studies. Meta-analyses were performed using MetaXL 5.3 with the quality effects model. Results: Screening of the article titles and abstracts yielded 134 full text articles for evaluation. Only three prospective studies that included appropriate data were considered for the final analysis. The relative risk of the CRBSI rate was 0.41 (0.14–1.17) for PICC vs. tunneled catheters. The relative risk of the CRBSI rate was 0.16 (0.04–0.64) for PICC vs. ports. The relative risk of the thrombosis rate was 3.16 (0.20–49.67) for PICCs vs. tunneled. Conclusions: There is insufficient evidence to show a difference in CRBSI rates between PICCs and tunneled catheters. On the other hand, PICCs showed lower CRBSI rates than ports. There was also no difference in the rate of catheter-related thrombosis and mechanical complications.