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Using perception of quality of life survey by Eurostat we construct the City Ecosystem Index (CEI)– a systemic indicator that measures subjective well-being in European cities. The purpose of the index is to inform public, policy-makers and entrepreneurs by providing a holistic view on subjective well-being across European cities. Once contrasted with the Global and Regional Systems of Entrepreneurship indices, which illustrate entrepreneurship environment in regions, we demonstrate that happiness of cities is associated with a higher entrepreneurial activity. CEI may be used as a control variable when predicting the level of entrepreneurship and entrepreneurial aspirations in cities.