Abstract: After the failure of the first entrepreneurship, why do some entrepreneurs give up while others restart? The study aims to explore the effects of a new, understudied imprint — the first entrepreneurial event — on serial entrepreneurship. Based on the imprinting theory, this paper first explores the negative effect of entrepreneurial failure on serial entrepreneurship, and then discusses how features of sensitive period and stamps of the environment during the genesis of imprinting affect the decay of imprinting. We explore the effects of four elements (failed entrepreneur’s age, the duration and the development stage of the failed entrepreneurial firm, as well as social tolerance) on serial entrepreneurship. The study uses the multi-regional data from China Labor-force Dynamic Survey to conduct the empirical study. The main findings are listed as follows: (1) the first entrepreneurial failure event has a negative effect on serial entrepreneurial activity. (2) The younger the entrepreneur ending the first failure event, the greater the likelihood of serial entrepreneurship. (3) The duration of the entrepreneurial failure event exhibits an inverted u-shaped relationship on serial entrepreneurial activity. (4) When the entrepreneurial failure event happens in the firm’s growth stage (compared with ending in the introductory stage and the maturity stage), the likelihood of serial entrepreneurship is higher. (5) When the first entrepreneurial failure event occurred in a more tolerant region, the likelihood of serial entrepreneurship is higher. The study also examines the gender differences of the effect of the first entrepreneurial failure event on serial entrepreneurship and finds that compared to male, female tends to be more sensitive to the first startup failure. This research applies the imprinting theory into entrepreneurship, and, for the first time, evaluates the profound impact of the first entrepreneurial event on entrepreneurs’ economic behaviors. Relevant research focused on the entities’ behaviors and environment during the metamorphosis of imprinting (the period after first startup ends), while this paper focuses on entrepreneurs and environment during the genesis of imprinting. Further, previous research analyzed the factors affecting serial entrepreneurship mainly from the perspectives of cognitive, risk perception, attribution and learning, while ignored the previous entrepreneurial imprinting. Consequently, this paper enriches the research perspectives of both imprinting theory and serial entrepreneurship. Moreover, this study sheds light on how entrepreneurs escape the entrepreneurial failure trap and move forward, and also provide insights on how government promotes high-quality entrepreneurial activities. Firstly, the government could strengthen the education to improve the entrepreneurial skills, support the media and the public to objectively understand the difficulties of entrepreneurship, and improve the public’s tolerance to failure, which may relieve entrepreneurs’ social pressure and, further, bring their startup experience into full play. Secondly, besides supporting novice entrepreneurs, the government should also pay attention and provide more support on experienced serial entrepreneurs. Finally, entrepreneurs’ failure stories and inspiring experiences could be shared by media, which may promote the sustainable development of the healthy entrepreneurial ecosystem.