To determine the risk factors for Deliberate Self-Harm [DSH] in patients presenting to the Emergency Departments [EDs] of three tertiary care hospitals of Karachi, Pakistan. Multicentre matched case control study. EDs of the Aga Khan University Hospital, Karachi, Civil Hospital, Karachi and Jinnah Postgraduate Medical Centre, Karachi, from March 2011 to February 2012. A total of 201 cases and 201 matched controls were taken from three hospitals situated in Karachi. All patients of 16 years and above presenting to the EDs of the hospitals with DSH attempt were invited to participate in the study. Controls were ED patients with complaints other than DSH. A control was matched with case for hospital, gender and age. Two questionnaires were used to collect information on the risk factors of DSH. Conditional Logistic Regression [CLR] was used to assess the association of various risk factors with DSH. Risk factors of DSH in Karachi included current history of mental disorder [OR = 4.53, 95% CI = 1.59 – 12.92] , not sharing problems with someone [OR = 4.67, 95% CI = 2.4 – 9.0] , living in rented houses [OR = 2.58, 95% CI = 1.37 – 4.84] , Pathan ethnicity [OR = 5.05, 95% CI = 1.01-25.38] followed by others [OR = 3.88, 95% CI = 0.77 – 19.69] and Urdu speaking [OR = 2.71, 95% CI = 0.59 – 12.45] . Absence of physical illness in the past month had an inverse association with DSH [OR = 0.17, 95% CI = 0.07 – 0.37] . Mental illnesses, low socio-economic status and loneliness were the risk factors of DSH patients presenting to the three EDs of Karachi. Physical illness in the last month was protective against DSH in these patients. Psychiatric evaluation of DSH patients in the ED is important for early diagnosis and management of mental disorders