Measuring the health status of individuals or a population is an important first step in the assessment of health care needs and the evaluation of the impact of health interventions. Reliable population-wide statistics on the health status are scarce especially in developing countries including Ghana. This paper assesses the validity and reliability of a standard instrument widely used in high income countries, the Short Form-36, as a tool to evaluate health status among women age 20 years and older in urban Ghana. The study draws on a representative sample of 2’814 respondents from the Women’s Health Study of Accra. We used multi-trait, multi-item matrix methods, Cronbach’s alpha estimates, half-split reliability tests and principal component analysis to evaluate the validity of SF-36 in the Ghanaian context. The response rate and the rate of completion for each health domain was over 97%. Item-level validation satisfied the rigorous psychometric criteria for internal consistency and reliability was above the suggested 0.40 criterion for all SF-36 scoring items apart from one item under Vitality sub-scale. The normed SF-36 scores showed wide variability and acceptable internal consistency (Cronbach’s alpha > 0.70). Following simple orthogonal rotation two principal components were identified and interpreted as Physical and Mental health components, identical to those found in other study settings. These components accounted for 62.6% of the reliable variance in scale scores across the study population. The absence of strong correlations between the various eight SF-36 sub-scales, demonstrate that each scale measures a distinct concept of health. The study provides evidence that SF-36 is suitable for the assessment of health status among women in Accra and, by extension, suitable for assessment of the health status of women in urban areas of Ghana.