Dental mortality has been reported by longitudinal studies on periodontal maintenance therapy (PMT), but the independent effect of smoking on tooth loss (TL), adjusted for important confounding variables, has been poorly evaluated. This systematic review aimed to assess and analyze the isolated effect of smoking TL among individuals undergoing PMT. Electronic, manual, grey literature, and recent articles (from April 2018) were searched, with no restriction regarding language; respective dates of publication were included. Epidemiological clinical studies reporting TL data among smokers undergoing PMT in comparison to nonsmoker control groups were selected. Methodological quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed, as well as I2 heterogeneity and sensitivity tests. Evidence quality was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Eleven papers were included in the systematic review: four case-control and seven cohort studies. Ten out of the 11 studies concluded that smoking was an important risk factor for the occurrence of TL. Meta-analysis of four of the cohort studies found that smokers had 3.24 times the chance of occurrence of TL than nonsmokers undergoing PMT (95%CI: 1.33-7.90). Overall, studies' risk of bias was low. The quality of the scientific evidence moderately supports that smokers undergoing PMT have a greater chance of TL than nonsmokers.