Purpose The current article presents data from 2 studies on clinical groups of children referred for speech assessment. The aims of these studies are to validate the Computer Articulation Instrument (CAI) with the known-group validation method and to determine the differential diagnostic power of the resulting speech profiles. Method Study 1 examined known-group validity by comparing the scores of 93 children diagnosed with speech-language difficulties on the picture naming (PN) task of the CAI with intelligibility judgments given by speech-language pathologists. In Study 2, the speech profiles of 41 children diagnosed with speech sound disorders (SSDs), consisting of 4-6 factor scores extracted from the 4 tasks of the CAI, namely, PN, nonword imitation (NWI), word and nonword repetition, and maximum repetition rate (MRR), were validated against clinical judgments of severity of the SSD given by speech-language pathologists. Results In Study 1, a repeated-measures analysis of variance revealed a significant effect of intelligibility level on the PN performance of the CAI and there were highly significant correlations between intelligibility and PN performance in the expected direction. Neither intelligibility level nor PN performance was related to nonverbal intelligence and language scores. The analysis of variance and a series of t tests in Study 2 revealed significant differences between the moderate and severe groups for the CAI factors based on PN and NWI and the bisyllabic and trisyllabic sequences of MRR, but not for the factor word and nonword proportion of whole-word variability based on word and nonword repetition, and the monosyllabic sequences of MRR. These results suggest that, especially, the tasks PN, NWI, and the bisyllabic and trisyllabic sequences of MRR are most sensitive for diagnosing SSDs. Conclusions The findings of these 2 studies support the known-group validity of the CAI. Together with the results of a previous study of our group on reliability and validity ( van Haaften et al., 2019 ), we can conclude that the CAI is a reliable and valid tool for assessment of children with SSDs.