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Background: This study aims to investigate association between peri-implant maintenance therapy (PIMT) and the frequency of peri-implant diseases and to further identify factors that contribute to failure of PIMT compliance.Methods: A cross-sectional study on patients who were healthy and partially edentulous was conducted. They were grouped in the following categories according to PIMT compliance: 1) regular compliers (RC) (≥2 PIMT/year); 2) erratic compliers (EC) (<2 PIMT/year); and 3) non-compliers (NC) (no PIMT). Radiographic and clinical analyses were carried out including probing depth (PD), plaque index (PI), bleeding on probing (BOP), mucosal redness (MR), suppuration (SUP), keratinized mucosa dimension, and marginal bone loss. A multiple logistic regression model was estimated at implant and patient level to obtain adjusted odds ratios (ORs) and to control possible confounding effects among variables.Results: Overall, 206 implants in 115 patients fulfilled inclusion criteria. At patient level, it was shown that association between compliance and peri-implant condition was statistically significant (P = 0.04). Compliance was associated with 86% fewer conditions of peri-implantitis. The probability of PIMT compliance was substantially associated with frequency of peri-implantitis (OR = 0.13, P = 0.01). Patients with a history of periodontal disease multiplied their probability of being EC (versus NC) 4.23 times with respect to not having a history of periodontal disease (P = 0.02). Moreover, light smokers significantly resulted to be NC compared with RC (P = 0.04) and EC (P = 0.02). Nevertheless, mucositis was not found to be statistically associated with level of compliance. In addition, PD, PI, BOP, MR, and SUP varied significantly according to PIMT compliance and peri-implant condition.Conclusions: Peri-implant maintenance compliance ≥2 PIMT/year seems to be crucial to prevent peri-implantitis in healthy patients. Furthermore, history of periodontal disease and disease severity, as well as its extent and a smoking habit, appear to be factors that influence the compliance risk profile (NCT02789306). [ABSTRACT FROM AUTHOR]