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Abstract: Spin-off companies are among the most crucial factors contributing to the productivity and development and cycles of innovation in developed and developing communities. Due to this importance, some reference groups in the field deem spin-off companies as the most effective links between science and marketplace, and hence, they have widely researched the field of spin-off companies. In the present paper, the problems acting against spin-off companies in Science and Technology Park of University of Tehran are investigated through a combined approach, specifying these factors in the light of the results of the research. The first step in the research is interviews with 15 people responsible for the foundation of the companies. According to data provided by the interviews, it was concluded that the answers provided by the interviewees are consistent. These answers were codified and the factors of failure were identified. In the qualitative section of the study, the researcher-made questionnaire, whose validity was confirmed by the qualified reference groups, was used to collect data. Then, factors of failure were distributed in hierarchies. The final section of the study included the interpretation and analysis of the results