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Introduction: Transgender women (TGW) are one of the most vulnerable groups, including higher prevalence of HIV and mental health disorders, such as anxiety and depression than in the general population. Major Depression Disorder (MDD) is one of the most important mental health conditions due to an increasing trend in prevalence in the general population. This study aims at describing the prevalence of symptoms of MDD (SMDD) and associated factors among TGW in capitals of three States in Northeast Brazil. Methods: TGW n = (864) were selected from the cities of Salvador (n = 166), Recife (n = 350), and Fortaleza (n = 348) using Respondent Driven Sampling methodology. Symptoms of MDD were defined according to the Patient Health Questionnaire-9 scale. Multinomial logistic regression was used to compare those with mild/moderate or moderately severe/severe symptoms of depression with those with no depression, respectively, using complex sample design. Weighted Odds Ratio with 95% confidence interval were estimated. Results: 51.1% of the sample was classified as mild/moderate and 18.9% as moderately severe/severe SMDD. Mild/moderate SMDD was associated with a history of sexual violence (OR = 2.06, 95%CI: 1.15–3.68), history of physical violence (OR = 2.09, 95%CI: 1.20–3.67),) and poor self-rated quality of life (OR = 2.14, 95%CI: 1.31–3.49).). Moderately severe/severe SMDD was associated with history of sexual violence (OR = 3.02, 95%CI: 1.17–7.77), history of physical violence (OR = 4.34, 95% CI:1.88–6.96), poor self-rated quality of life (OR = 3.32, 95%CI:1.804–6.12), lack of current social support (OR = 2.53, 95%IC: 1.31–4.88) and lack of family support in childhood (OR = 2.17, 95%IC 1.16–4.05)). Conclusions: Our findings strengthens the evidence of a higher prevalence of SMDD among TGW as compared to the general population. Public health policies and actions that target social determinants of risk and protection for MDD among TGW must be urgently implemented. [ABSTRACT FROM AUTHOR]