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Integrating generative artificial intelligence (GenAI) into professional practice has become an important topic for professional instructional design practice and training. Accordingly, the purpose of this multiple-case study was to examine six professional instructional designers’ integration of GenAI into their professional practice and the factors affecting this integration. Research data were collected through semi-structured interviews conducted with professional instructional designers working in corporate or higher education settings. The results were as follows: (a) instructional designers mostly integrate GenAI into instructional design and/or development phases and they think that it also has the largest impact on these two phases; and (b) instructional designers’ integration of GenAI into their professional practice is mainly based on their ambivalent attitudes toward it, which is closely linked to the advantages and disadvantages associated with the technology. Specifically, instructional designers’ basic understanding of GenAI, the efficiency of generating instructional content through GenAI, the inaccuracy of GenAI-created products, instructional designers’ use of GenAI in everyday life, and institutional or company support shape their attitudes towards and integration of GenAI into their professional practice. All these findings suggest that instructional design and development phases are especially vulnerable to and can benefit from instructional designers’ attitudes and use of GenAI. Accordingly, it can be useful to address and enhance attitudes toward GenAI technology in instructional design training, which can promote instructional designers’ acceptance of the technology and effective use of it.