Objective: The Inuit population in Canada's North has suffered from high rates of death by suicide. We report on the first large-scale, controlled, epidemiologically representative study of deaths by suicide in an Indigenous population, which investigates risk factors for suicide among all Inuit across Nunavut who died by suicide during a 4-year period. Methods: We identified all suicides by Inuit (n = 120) that occurred between January 1, 2003, and December 31, 2006, in Nunavut. For each subject, we selected a community-matched control subject. We used proxy-based procedures and conducted structured interviews with informants to obtain life histories, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I and II diagnoses, and measures of impulsive and (or) aggressive traits. Results: Compared with control subjects, subjects who died by suicide were more likely to have experienced childhood abuse (OR 2.38; 95% CI 1.39 to 4.08), have family histories of major depressive disorder (P = 0.002) and suicide completion (P = 0.02), and have been affected by major depressive disorder (OR 13.00; 95% CI 6.20 to 27.25), alcohol dependence (OR 2.90; 95% CI 1.59 to 5.24), or cannabis dependence (OR 3.96; 95% CI 2.29 to 6.8) in the last 6 months. In addition, subjects who died by suicide were more likely to have been affected with cluster B personality disorders (OR 10.18; 95% CI 3.34 to 30.80) and had higher scores of impulsive and aggressive traits (P < 0.001). Conclusions: At the individual level, clinical risk factors for suicide among Inuit are similar to those observed in studies with the general population, and indicate a need for improved access to mental health services. The high rate of mental health problems among control subjects suggests the need for population-level mental health promotion.