Among transgender binary and nonbinary/queer (TNBQ) individuals, perceived stigma has been documented to be significantly associated with health disparities that diminish overall quality of life. The present study examined the serial mediating roles of patient-provider relationship quality and perceived barriers to care in the association between perceived stigma and quality of life among TNBQ individuals residing in Italy. Data were collected from 132 TNBQ participants aged 18-60 years ( = 28.52, = 8.57) through an online survey assessing perceived stigma, patient-provider relationship quality, perceived barriers to care, and quality of life. A serial mediation model was analyzed using Model 6 of the SPSS Macro Process, version 29, and separately applied to two subgroups of TNBQ participants (i.e., binary and nonbinary) to detect potential differences. Findings indicated that in both groups (i.e., binary and nonbinary populations), when considered independently, only perceived barriers to care-but not patient-provider relationship quality-mediated the relationship between perceived stigma and quality of life. A serial mediation effect was also observed, wherein the relationship between perceived stigma and quality of life was mediated sequentially through patient-provider relationship quality and barriers to care, but only for the binary group. These findings hold significant clinical relevance, as improving the perceived quality of patient-provider relationships may help reduce perceived barriers to healthcare access. In turn, this may attenuate the detrimental effects of perceived stigma on the quality of life among TNBQ individuals.