This retrospective clinical study compared two different professional maintenance therapy (MT) approaches (with and without periodic removal and decontamination of prosthetic components) on peri-implant inflammatory clinical and biochemical parameters after 5 years of implant function. A retrospective analysis based on patient records was used to assess inflammatory clinical and biochemical parameters around dental implants placed by the same clinician in a private practice. The Plaque Index (PI), peri-implant probing depth (PPD), mucosal recession (REC), bleeding on probing (BOP), and radiographic marginal bone level were determined at baseline and at each follow-up year. Moreover, at the last follow-up visit, the peri-implant intrasulcular levels of active metalloproteinasis 8 (aMMP-8) were also assessed. All participants were under MT with a 6-month recall interval. A total of 92 patients with 132 implants were selected. At the end of the study period, 12 patients with 12 implants were classified as dropouts. The remaining 80 patients and 120 implants were classified into two groups: Group 1 (42 patients, 62 implants) received MT with periodic removal and decontamination of prosthetic components; Group 2 (38 patients, 58 implants) received MT without periodic removal and decontamination of prosthetic components. No statistical differences were found between the groups regarding PI, PPD, and REC. Group 1 presented a statistically significant higher number of sites with BOP (12.4% vs 6.2%). Marginal bone loss was statistically higher in Group 2 than in Group 1 (0.23 ± 0.6 mm vs 0.78 ± 0.3 mm). Intrasulcular levels of aMMP-8 were statistically higher in Group 1 than in Group 2. The supplemental application of periodic removal and decontamination of prosthetic components during MT had a significantly positive effect on the inflammatory status of peri-implant tissues.