Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.