Introduction: Manganese (Mn) toxicity is often observed in adult patients receiving long-term home parenteral nutrition (HPN), and differing recommendations on the safe level of Mn administration to these patients have been made in the literature over the past 10 years. Methods: This systematic review used the National Health and Medical Research Council (NHMRC) evidence hierarchy to assess the design and strength of individual studies (high I to low IV) and the overall grade of evidence (grade A high to grade D low). Results: Eight studies met the inclusion criteria. Levels of evidence ranged from high (NHMRC II) to mid-level (III-3). A widespread recommendation in the literature for patients receiving long-term HPN is 55 μg (1 μmol) Mn/d. Conclusion: The recommendation of 55 μg (1μmol) Mn/d is of moderate-strength evidence (NHMRC B grade). There is limited evidence to support not supplementing Mn to patients receiving long-term HPN. Further intervention studies providing high-level evidence (II and above) are required to determine the safety of not supplementing Mn to all patients receiving long-term HPN.