This book constitutes the refereed proceedings of the 52nd International Simulation and Gaming Association Conference, ISAGA 2021, held in Indore, India, during September 6–10, 2021.  The 24 full papers included in this book were carefully reviewed and selected from 58 submissions. They were organized in topical sections as follows: game design and facilitation; gaming in education; player experience in simulations; and policy formulation and serious games.