Background: Individuals with MDD differ from non-depressed individuals upon measures of dimensional personality traits. It is found that there has been a complex and variable association between personality and depression. We can decide treatment plan, course of treatment, and prognosis based on this knowledge. Aims: To study the Big Five Personality Traits in Patients of Major Depressive Disorder. Methods: A cross-sectional study was conducted at a tertiary care hospital at the Department of Psychiatry. 100 patients were taken. Personality traits were assessed using the Big Five Inventory focused on domains like Neuroticism, Extraversion, Openness to experience, Agreeableness, and Conscientiousness. The severity of depression was assessed using Hamilton Depression Rating Scale. Other appropriate variables were obtained using semi-structured proforma. Data was analyzed with SPSS Epi Info™ v7.2.5. Linear correlation between two continuous variables was explored using Pearson’s correlation (if the data were normally distributed) and Spearman’s correlation (for non-normally distributed data). Statistical significance was kept atp < 0.05. Results: Correlation of Big Five personality traits was studied with respect to various socio-demographic and clinical variables. Conclusion: Personality trait Neuroticism may be a risk factor in developing major depression. Extraversion, Openness to experience, Agreeableness and Conscientiousness may be associated with some protective effect. An individual-tailored approach to management is advisable for better long-term outcomes based on personality traits.