Introduction The Short Form Survey 12-item (SF12) mental and physical health version has been applied in several studies on populations from Sub-Saharan Africa. However, the SF12 has not been computed and validated for these populations. We address in this paper these gaps in the literature and use a health intervention example in Malawi to show the importance of our analysis for health policy. Methods We firstly compute the weights of the SF12 physical and mental health measure for the Malawian population using principal component analysis on a sample of 2838 adults from wave four (2006) of Malawian Longitudinal Study of Aging (MLSFH). We secondly test the construct validity of our computed and the US-population weighted SF12 measures using regression analysis and Fixed Effect estimation on waves four, seven (2012) and eight (2013) of the MLSFH. Finally, we use a Malawian cash transfer programme to exemplify the implications of using US- and Malawi-weighted SF12 mental health measures in policy evaluation. Results We find that the Malawian SF12 health measure weighted by our computed Malawian population weights is strongly associated with other mental health measures (Depression:-0.501, p = < 0.001; Anxiety:-1.755; p = < 0.001) and shows better construct validity in comparison to the US-weighted SF12 mental health component (rs = 0.675 versus rs = 0.495). None of the SF12 measures shows strong associations with other measures of physical health. The estimated average effect of the cash transfer is significant when using the Malawi-weighted SF12 mental health measure (treatment effect: 1.124; p = < 0.1), but not when using the US-weighted counterpart (treatment effect: 1.129; p > 0.1). The weightings affect the size of the impacts across mental health quantiles suggesting that the weighting scheme matters for empirical health policy analysis. Conclusion Mental health shows more pronounced associations with the physical health dimension in a Low-Income Country like Malawi compared to the US. This is important for the construct validity of the SF12 health measures and has strong implications in health policy analysis. Further analysis is required for the physical health dimension of the SF12.