Aripiprazole is approved in different countries as treatment for several mental disorders, but its transdiagnostic potential has not yet been assessed according to established criteria such as the recently proposed TRANSD criteria. The present work aims to test whether aripiprazole monotherapy could be considered a transdiagnostic intervention. An umbrella review of meta-analyses of randomized controlled trials (RCTs) of aripiprazole monotherapy vs placebo was conducted for any disorder defined according to standard diagnostic criteria. Primary outcomes were levels of psychiatric disease-specific symptoms. TRANSD criteria were applied to assess transdiagnosticity, while the AMSTAR-2 tool was used to assess the quality of eligible meta-analyses. Four pairwise meta-analyses and three network meta-analyses were included, consisting of 25 RCTs of aripiprazole monotherapy vs. placebo (N = 5469). Aripiprazole outperformed placebo on primary outcomes in Alzheimers disease with behavioral disturbance (AD) (neuropsychiatric symptoms SMD 0.20, 95%CI 0.05-0.35, max 15 mg/day), autism spectrum disorder (ASD) (severity of symptoms SMD 0.39, 95%CI 0.30-0.48, max 15 mg/day), bipolar I disorder (BD) (severity of manic symptoms SMD 0.30, 95%CI 0.12-0.47, max 30 mg/day), and schizophrenia/schizoaffective disorder (response rate RR 0.84, 95%CI 0.78-0.92, max 30 mg/day). TRANSD criteria were met (pooled SMD 0.25, 95%CI 0.09-0.41) across these disorders Quality was high in all the included meta-analyses according to AMSTAR-2. According to TRANSD criteria, aripiprazole monotherapy is a (dose-specific) transdiagnostic intervention to treat psychiatric disease-specific symptoms across 5 diagnoses (AD, ASD, BD (mania), schizophrenia/schizoaffective disorder), across four DSM-5 diagnostic groups (neurocognitive disorders, neurodevelopmental disorders, bipolar and related disorders, schizophrenia spectrum and other psychotic disorders). (c) 2020 Elsevier B.V. and ECNP. All rights reserved.