At the present time, peri-implantitis has become a global burden that occurs with a frequency from 1% to 47% at implant level. Therefore, we aimed herein at assessing the impact of peri-implant maintenance therapy (PIMT) on the prevention of peri-implant diseases. Electronic and manual literature searches were conducted by 3 independent reviewers using several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register, for articles up to June 2015 without language restriction. Articles were included if they were clinical trials aimed at demonstrating the incidence of peri-implant diseases under a strict regime or not of PIMT. Implant survival and failure rate were studied as secondary outcomes. A meta-analysis was conducted to evaluate the influence of PIMT and other reported variables upon peri-implant diseases. Thirteen and 10 clinical trials were included in the qualitative and quantitative analysis, respectively. Mucositis was affected by history of periodontitis and mean PIMT at implant and patient levels, respectively. Similarly, significant effects of history of periodontal disease were obtained for peri-implantitis for both implant and patient levels. Furthermore, mean PIMT interval was demonstrated to influence the incidence of peri-implantitis at implant but not patient level. PIMT interval showed significance at both levels. For implant survival, implants under PIMT have 0.958 the incident event than those with no PIMT. Within the limitations of the present systematic review, it can be concluded that implant therapy must not be limited to the placement and restoration of dental implants but to the implementation of PIMT to potentially prevent biologic complications and hence to heighten the long-term success rate. Although it must be tailored to a patient’s risk profiling, our findings suggest reason to claim a minimum recall PIMT interval of 5 to 6 mo. Additionally, it must be stressed that even in the establishment of PIMT, biologic complications might occur. Thus, patient-, clinical-, and implant-related factors must be thoroughly explored.