: To investigate the effectiveness and safety of brexpiprazole as an adjunctive treatment to antidepressant therapy (ADT) in Asian adults with major depressive disorder (MDD) and inadequate response in a real-life clinical setting in Singapore. : This was a prospective, observational 3-month study of patients with MDD who had brexpiprazole added to their existing ADT. The study was conducted at two sites in Singapore between September 2020 and October 2021. The co-primary endpoints were Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression-Severity (CGI-S). Other endpoints included Clinical Global Impression-Improvement (CGI-I), Sheehan Disability Scale (SDS), Generalized Anxiety Disorder 7-item scale (GAD-7), and safety. : Twenty patients were enrolled and 16 completed the study. There were improvements in PHQ-9, CGI-S, SDS, and GAD-7 scores from baseline at Week 12, with a mean difference of -4.8, -1.3, -8.5, and -6.2, respectively. The CGI-I score improved from baseline with a mean score of 2.3 at Week 12. One third achieved response and 25% achieved remission based on PHQ-9 scores at Week 12. Similar results were obtained using CGI-S scores (38% for both). The incidences of adverse events (AEs) and treatment-related AEs were 55% (11/20) and 50% (10/20), respectively. There were no deaths or severe AEs. Two patients withdrew brexpiprazole during the study. : The observed effects and safety of adjunctive brexpiprazole in Asian adults with MDD in the real-world setting in Singapore were consistent with those from clinical trials.