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This study was aimed at looking into the microbiological/inflammatory parameters predicting the periodontal success/failure of fixed prostheses. Microbiological and inflammatory patterns were studied at 102 sites having metaloceramic crowns in place from 3 to 6 years and divided in healthy sites (HS), gingivitis affected (MG), and periodontitis affected (PB). Total bacterial flora and selected indicator species in subgingival plaque were quantified by quantitative real-time PCR. The concentrations of IL-1β, IL-6, and TNF-α were determined in gingival crevicular fluid (GCF) by enzyme-linked immunosorbent assays. The experimental sites showed no significant difference with respect to the age and gender of the patients and to the position of the crown margins. Poor marginal adaptation was significantly higher in MG and PB. The total amounts of bacteria per probing depth showed no significant differences among the three groups and their controls, while both MG and PB sites showed altered patterns in the distribution of specific bacteria. Both MG and PB sites showed significantly higher levels of inflammatory cytokines in GCF. The control teeth of PB subjects showed significantly higher levels of IL-1β as compared to other control sites. Data confirm that the application of metaloceramic crowns is a factor of risk for the development of gingival/periodontal inflammation. This risk is possibly associated with microbiological and host factors that predispose to the onset of periodontal alterations at sites reconstructed with metaloceramic crowns. These factors, once their role is confirmed by longitudinal studies, could be used to set up rapid tests to early predict the onset of periodontal disease at reconstructed sites.