Objective: To validate a two-item food security questionnaire (FSQ) for use in a clinical setting to screen HIV-1 infected patients for food insecurity. Design: The present study was a questionnaire-based survey of forty-nine subjects attending an HIV clinic. Subjects completed a two-item questionnaire and a six-item validated FSQ contemporaneously. Results: A strong correlation was found between the two-item and six-item FSQ (r50?895; 95% CI 0?821, 0?940; P,0?0001). Cronbach’s a coefficient was found to be 0?94 and 0?90 for the two-item and six-item FSQ, respectively. The two-item FSQ yielded a sensitivity of 100% (95% CI 75, 100) and a specificity of 78% (95% CI 61, 90). The negative predictive value was found to be 100% (95% CI 88, 100). Conclusions: The results of the present study suggest that the two-item FSQ is a valid, reliable and sensitive screening tool of food insecurity in people living with HIV in a clinical setting.