BACKGROUND Several studies have revealed significant differences between bipolar (BP) and unipolar depression (UP). Misdiagnosing BP depression results in suboptimal symptom resolution, induction of manic switch, mixed state, or accelerated cycling. This study compares various psycho-socio-demographic, longitudinal course, and phenomenological factors associated with BP and UP depression. MATERIALS AND METHODS We compared 30 UP and 30 BP depression patients using a specially designed intake proforma, International Classification of Diseases-10 diagnostic criteria for research, Hamilton Rating Scale for Depression-21 (HAMD-21), Hypomania Checklist-32 Questionnaire (HCL-32), Brief psychiatric rating scale (BPRS), and Kuppuswami's socioeconomic status scale. RESULTS BP depression group consisted of mostly males, with earlier age of onset of illness, longer illness duration, frequent episodes, hospitalizations and psychotic symptoms. The total HAM-D score and 4 HAM-D item scores-psychomotor retardation, insight, diurnal variation of symptoms and its severity, and paranoid symptoms were significantly higher in this group. Binary logistic regression identified the age of onset, the total duration of illness, frequency of affective episodes, and presence of delusions as predictors of bipolarity (odds ratio = 1.327; 1.517; 0.062; 0.137). CONCLUSIONS Identification of clinical markers of bipolarity from large scale prospective studies is needed.