The following paper analyses whether becoming self-employed can help to reduce the vulnerability to poverty of rural households. We use data collected during four survey waves in three rural provinces in Vietnam to calculate region-specific logistic panel regressions. The results show that becoming self-employed increases the likelihood of poor households escaping poverty, but only if they are located in a regional economic environment characterized by an advanced stage of structural change, good infrastructural conditions, and proximity to markets. In less well-developed regions, becoming self-employed is not sufficient to increase the probability of poor households escaping poverty. What matters more is that self-employment is driven by opportunity and not by necessity. However, even opportunity-driven self-employment does not guarantee a reduction of vulnerability to poverty in all regional settings and for all household types. Especially, regional overspecialization in cash-crop production and inequality in access to assets have to be taken into account. In times of declining commodity prices, self-employment entails a risk of business failure in regions that are overspecialized in cash-crop production. For households whose initial investment is high and whose endowment with social and educational assets is low, this can result in increased vulnerability to poverty.