The oral cavity is naturally colonized by a large number of different microbial species that are in a state of equilibrium. Dysbiosis can be caused by either changes in local or systemic conditions and is associated with increased risk of caries, periodontal disease, oral cancer and systemic diseases such as diabetes, cardiovascular disease, etc. Use of dental implants for rehabilitation of fully edentulous patients or those with terminal dentition is now a common practice. However, little is known on the influence of prosthetic material of full-arch implant supported fixed prostheses on overall salivary oral microbial profiles. Additionally, the significance of removing and cleaning the prosthesis at recall visits on the microbiome is yet to be determined. This study compares salivary microbiomes in subjects with either a zirconia or acrylic-metal prosthesis. Completely edentulous subjects rehabilitated for at least 1 year with either a zirconia or acrylic-metal full-arch implant supported fixed prosthesis were included. Stimulated salivary samples were collected with the prostheses in place at baseline prior to removal and cleaning of the prosthesis and after 1 week, 1 month and 3 months following cleaning. Oral microbiome changes were assessed using 16S rRNA gene high throughput sequence analysis with QIIME2 to obtain Amplicon Sequence Variants which by using the Human Oral Microbiome Database (HOMD) are converted to relative levels of bacterial taxa. Gain or loss of microbes and changes in abundance and diversity during treatment were evaluated. Alpha and beta diversity analyses were performed to determine changes in salivary microbiome with cleaning and differences due to clinical factors. Salivary microbial profiles were compared among the different superstructures and longitudinally with time after cleaning the prosthesis. Associations with clinical assessment parameters were also evaluated to determine if the salivary microbiota reflects the clinical condition of the dental implants. For this, the following parameters were collected at baseline: bleeding on probing, probing depths and marginal bone loss. Subjects with signs of peri-implant disease such as bleeding on probing and marginal bone loss are anticipated to have a salivary microbial profile reflective of diseased state with higher red and orange complex bacteria. Our study found that the number of species of bacteria decreases after prostheses are cleaned. There is a lower number of species in the saliva of those with zirconia prostheses which is consistent with the prosthesis being cleaner. In addition, bacteria were identified to be different between the zirconia versus acrylic prostheses. Lastly, no significant differences were noted when determining bacterial taxa associated with peri-implant health versus disease. Therefore, few overall differences were dependent on the presence of peri-implant disease. The results of this study support a concrete decision-making process for choosing appropriate implant supported prostheses for edentulous patients and possible benefit of removing the prosthesis for cleaning. On the treatment side, perhaps we could selectively target and block functional pathways that are essential to those taxa identified as differentially abundant in peri-implant disease?