Purpose: The All-on-4 treatment concept has been shown to be an effective clinical procedure; however, to date, no studies have analyzed the subgingival microbiota present in these restorations. The purpose of this study was to evaluate the microbial profile of the subgingival biofilm around dental implants placed in the All-on-4 protocol and compare the microbial profile around axial and tilted implants. Materials and Methods: Fourteen subjects treated by the All-on-4 concept were evaluated clinically and microbiologically. Subgingival biofilm was collected from each patient, and the amount of 40 species of bacteria was assessed using the checkerboard DNA-DNA hybridization technique. Results: The results for the indices of probing depth (PD), bleeding on probing, marginal bleeding, and visible plaque were 2.32 mm, 46%, 60%, and 57%, respectively. Tilted implants presented a significantly higher mean PD and Plaque Index compared with axial implants (P .05). Fusobacterium nucleatum ssp vincentii, Veillonella parvula, and Fusobacterium nucleatum ssp polymorphum were found in higher levels; however, no difference in the microbial composition was observed between tilted and axial implants (P > .05). Tilted implants presented statistically higher mean levels for the orange complex in relation to the axial implants (P .05). Conclusion: Despite the clinical success rate of the All-on-4 protocol, the subgingival biofilm of tilted implants presented a higher proportion for the orange complex pathogens in comparison to axial implants. These data could suggest that subjects with this modality of implant-supported restoration must be aware that they need a more rigorous maintenance protocol. Keywords: All-on-4, dental implant, microbiota, prosthesis, subgingival biofilm