A retrospective cohort design was used to assess the long-term clinical effectiveness of systemic amoxicillin and metronidazole, used adjunctively with non-surgical peri-implantitis treatment (NST) and whether it prevents the need for further surgical interventions. Of the 57 peri-implantitis patients examined, 45 patients were included in this study. The participants were divided into two subgroups in accordance to who had received NST with or without systemic antibiotics. Selection was based on prior participation in a three-month randomised control trial, ensuring comparability of data regarding peri-implantitis severity and treatment history. Data were extracted pre-treatment, 3-months post-treatment and at a long-term follow-up interval of 36 months. The primary outcome was the need for additional surgical intervention and was analysed via Kaplan-Meier analysis and Cox regression. A multitude of secondary clinical outcomes were evaluated using parametric and non-parametric tests, including peri- implant probing depth, bleeding scores and treatment success. Overall, 62.2% of the 45 NST patients did not need surgical peri-implantitis treatment: 73.9% of the subgroup with antibiotics and 50% of the subgroup without antibiotics respectively. However, the difference between the two groups was not statistically significant (log-rank test, p = 0.110). The Cox regression analysis also displayed no significance over the first three years post-treatment (p = 0.115). Additionally, the study found that deeper peri- implant pockets at baseline significantly predicted the need for future surgical treatment (p = 0.031), highlighting the importance of initial disease severity in treatment outcomes. The study concludes that the adjunctive use of systemic amoxicillin and metronidazole with NST may delay but not statistically reduce or prevent a future surgical need. Although a short-term reduction in clinical inflammatory parameters was evident, the long-term effectiveness in altering the progression of peri-implantitis remains limited.