There is a widespread belief that poverty leads to the spread of HIV/AIDS. However, intra-country comparisons of the phenomenon have been limited. This study seeks to fill this gap by examining the relationship between poverty and HIV prevalence amongst the 10 administrative regions of Ghana. Based on the available data for poverty and HIV, certain distinct patterns emerge. For example, poverty levels are the highest in the three northern regions (Upper East, Upper West and Northern region) even though their HIV prevalence is one of the lowest. It clearly follows that there are more complex forces at work than just the effects of poverty alone. To unravel some of these puzzles, the paper proposes a key role for culture, globalization and geographical accessibility. In addition, it is suggested that local level studies in a multivariate framework have much to contribute to the identification and quantification of relevant relationships.