We aimed to (1) apply cluster analysis techniques to mixed-type data (numerical and categorical) from baseline neuropsychological standard and widely used assessments of patients with acquired brain injury (ABI) (2) apply state-of-the-art cluster validity indexes (CVI) to assess their internal validity (3) study their external validity considering relevant aspects of ABI rehabilitation such as functional independence measure (FIM) in activities of daily life assessment (4) characterize the identified profiles by using demographic and clinically relevant variables and (5) extend the external validation of the obtained clusters to all cognitive rehabilitation tasks executed by the participants in a web-based cognitive rehabilitation platform (GNPT). We analyzed 1,107 patients with ABI, 58.1% traumatic brain injury (TBI), 21.8% stroke and 20.1% other ABIs (e.g., brain tumors, anoxia, infections) that have undergone inpatient GNPT cognitive rehabilitation from September 2008 to January 2021. We applied the k-prototypes algorithm from the clustMixType R package. We optimized seven CVIs and applied bootstrap resampling to assess clusters stability (fpc R package). Clusters' post hoc comparisons were performed using the Wilcoxon ranked test, paired t-test or Chi-square test when appropriate. We identified a three-clusters optimal solution, with strong stability (>0.85) and structure (e.g., Silhouette > 0.60, Gamma > 0.83), characterized by distinctive level of performance in all neuropsychological tests, demographics, FIM, response to GNPT tasks and tests normative data (e.g., the 3 min cut-off in Trail Making Test-B). Cluster 1 was characterized by severe cognitive impairment (N = 254, 22.9%) the mean age was 47 years, 68.5% patients with TBI and 22% with stroke. Cluster 2 was characterized by mild cognitive impairment (N = 376, 33.9%) mean age 54 years, 53.5% patients with stroke and 27% other ABI. Cluster 3, moderate cognitive impairment (N = 477, 43.2%) mean age 33 years, 83% patients with TBI and 14% other ABI. Post hoc analysis on cognitive FIM supported a significant higher performance of Cluster 2 vs. Cluster 3 (p < 0.001), Cluster 2 vs. Cluster 1 (p < 0.001) and Cluster 3 vs. Cluster 1 (p < 0.001). All patients executed 286,798 GNPT tasks, with performance significantly higher in Cluster 2 and 3 vs. Cluster 1 (p < 0.001).