During the last two decades the world has seen an increase in the use of Hematopoietic Stem Cell Transplant (HSCT) which has led to its worldwide expansion. Since, HSCT unit is an advanced set up, developing and maintaining a successful hematopoietic stem cell transplant program with a properly functioning unit enhances the credibility of any tertiary level medical facility especially for a country like ours which is in its early expanding phase of providing transplant services. The underlying principle for designing any HSCT facility is to maintain the highest possible level of aseptic environment for patients undergoing the transplant in order to prevent healthcare associated infections. Basic premises of designing the entire HSCT unit was to ensure restricted access to the facility and having an aseptic environment by implementing infection control parameters in design elements, which are explained subsequently in the article. The present manuscript describes the project experience of creating a positive pressure isolation facility for HSCT patients at a tertiary care hospital, India, which is a resource limited setting with an emphasis on need assessment, key elements in planning and designing along with the challenges associated with it.