Background: HIV/AIDS patients are subjected to myriads of stressors, for which ability to cope with these stressors and exhibit resilient behaviors and positive outcomes may be very critical. Objectives: The aim of the study is to determine the prevalence of Major Depression among HIV/ AIDS Patients in Kano, to determine the level of resilience among individual HIV/AIDS patients in Kano, and to determine the relationship between individual’s resilience and development of depression. Design: The study was a descriptive cross sectional study. Setting: Aminu Kano Teaching Hospital (AKTH), North-western Nigeria. Subjects: Four hundred and two patients (402) were selected using systematic sampling methods from all the patients attending the HIV/AIDS clinic conducted by the Department of Internal Medicine of the hospital. The study was conducted over a period of 6 months (February-August) in 2012. Methods: The socio-demographic data was collected using a pre-tested semi-structured questionnaire. Thereafter, Resilience Scale (RS) and Hospital Anxiety and Depression scale (HADS) (depression sub-scale) were administered to the respondents to measure their resilience and screen for depression respectively. Those who scored 8 and above on the HAD scale were assessed for depression using MINI Plus. The effect of resilience on development of depression was evaluated after accounting for other confounding factors. Results: At the end of the study, 402 patients were recruited. There were slightly more females than males (51% compared to 49%), and a little over half of the participants were currently married. The age range was between 17 and 54 years with the mean age of 32.8 (sd = 7.5) years. Almost two thirds of the participants (63.4%) scored above the cut point for resilience on the Resilience scale. On diagnostic interview with MINI plus, 35.1% of the participants had major depressive disorder. Resilience was found to be strongly protective against depression among the patients, OR=0.07 (95 C.I -0.003-0.015, p < 0.0001). Those who perceived death as inevitable were 5 times more likely to have major depressive disorder, whereas having the experience of stigma increased the risk for major depressive disorder about 3 times. Participants whose CD4 count was less than 200 were about 6 times more likely to experience major depressive disorder (OR 5.8, 95%, C.I. 3.6 – 9.2). Having support greatly reduced the risk of major depressive disorder (OR 0.007, 95% C.I. = 0.003 – 0.02, p < 0.0001). Participants who had co-morbid diseases were more likely to have major depressive disorder, compared with those who had no co-morbid diseases (χ2 = 34.0, p < 0.001). Only resilience (p<0.001), support (p<0.001) and CD4 (p=0.04) count less than 200 are independent predictors of depression among the study subjects. Conclusion: Depression is highly prevalent among HIV/AIDS patients in AKTH, and is substantially related to resilience. This provides a vista for primary prevention of depression among HIV/AIDS patients by allowing for screening of resilience, and instituting appropriate preventive measures, especially among those with low resilience. Treatment in those discovered to be depressed will go a long way in improving their overall quality of life. In summary, these point to greater need for involvement of psychiatrists in holistic management of HIV/AIDS patients, and potentially in other chronic diseases. Key words: depression, resilience, HIV/AIDS, Aminu Kano Teaching Hospital, Nigeria