A cost analysis to compare high dose rate (HDR) brachytherapy using either californium-252 (252Cf) or 192Ir was performed to determine the prospects of widespread clinical implementation of HDR 252Cf. Interest in the neutron-emitting 252Cf radioisotope as a radiotherapy nuclide has undergone a resurgence given recent efforts to fabricate HDR remotely afterloaded sources, and other efforts to create a miniature source for improved accessibility to a variety of anatomic sites. Therefore, HDR 252Cf brachytherapy may prove to be a potential rival to the use of HDR 192Ir remotely afterloaded brachytherapy--the current standard-of-care treatment modality using HDR brachytherapy. Considering the possible improvements in clinical efficacy using HDR 252Cf brachytherapy and the enormous costs of other high-LET radiation sources, the cost differences between 252Cf and 192Ir may be well-justified.