© 2019 Christou et al. Objectives: The aim of this systematic review is to identify how different types of orthodontic interventions affect the esthetics of the smile, any time after orthodontic treatment. Materials and methods: A systematic search of the literature was carried out using 5 electronic databases (PubMed, Embase, The Cochrane Library, Scopus, Dentistry and Oral Sciences Source) that included articles until October 2017. Randomized and non-randomized controlled clinical trials, case–control observational studies, and cohort and cross-sectional studies with validated data collection and/or follow-up periods reporting on orthodontic interventions that changed the smile any time after orthodontic treatment were part of the study protocol. Only studies that were published in the English language and those that had human patients of any age and gender who underwent orthodontic treatment were included. Results: A total of 814 articles were found and 9 of them were included (7 cohort and 2 cross-sectional studies). Among the selected articles, 8 stated the type of orthodontic intervention used during treatment and 1 did not specify the intervention. Eight articles were judged of moderate risk and 1 had high risk of bias. Conclusion: Orthodontic treatment affects the esthetics of the smile in three dimensions. There was slight evidence that extractions do not affect the smile width and buccal corridors area. Evidence on palatal expansion was controversial. The remaining existing data evidence that investigated smile esthetics after orthodontic treatment was uncertain. Therefore, more validated, evidence-based studies are needed.