In order to design appropriate HIV prevention programs, it is important to examine the perception and knowledge of HIV/AIDS and methods of prevention. This article explores comprehensive knowledge of HIV/AIDS prevention methods among women and men in slum and non-slum areas in the National Capital Territory of Delhi, India. Data were drawn from the National Family Health Survey, 2005–06 (NFHS-3). The sample included 3096 women aged 15–49 years and 1321 men aged 15–54 years. Pearson Chi-square test and logistic regression analyses were conducted to examine the association between the study variables and the background characteristics of the slum and non-slum populations. Comprehensive knowledge of HIV/AIDS prevention methods was significantly lower among women and men in slum areas as compared with non-slum areas. Compared to men, women had less comprehensive knowledge of HIV/AIDS prevention methods in slum and non-slum areas, even after controlling for various demographic and socio-economic and exposure variables. Interventions are needed to build knowledge of HIV/AIDS transmission and prevention methods through mass media campaigns, and information, education and communication programs (IEC) on HIV/AIDS in slum areas.