Background: The Parent-Infant Relationship Global Assessment Scale (PIR-GAS) signifies a conceptually relevant development in the multi-axial, developmentally sensitive classification system DC:0-3R for preschool children. However, information about the reliability and validity of the PIR-GAS is rare. A review of the available empirical studies suggests that in research, PIR-GAS ratings can be based on a ten-minute videotaped interaction sequence. The qualification of raters may be very heterogeneous across studies. Methods: To test whether the use of the PIR-GAS still allows for a reliable assessment of the parent-infant relationship, our study compared a PIR-GAS ratings based on a full-information procedure across multiple settings with ratings based on a ten-minute video by two doctoral candidates of medicine. For each mother-child dyad at a family day hospital (N = 48), we obtained two video ratings and one full-information rating at admission to therapy and at discharge. This pre-post design allowed for a replication of our findings across the two measurement points. We focused on the inter-rater reliability between the video coders, as well as between the video and full-information procedure, including mean differences and correlations between the raters. Additionally, we examined aspects of the validity of video and full-information ratings based on their correlation with measures of child and maternal psychopathology. Results: Our results showed that a ten-minute video and full-information PIR-GAS ratings were not interchangeable. Most results at admission could be replicated by the data obtained at discharge. We concluded that a higher degree of standardization of the assessment procedure should increase the reliability of the PIR-GAS, and a more thorough theoretical foundation of the manual should increase its validity.