There is a high degree of uncertainty regarding the appropriate force level that should be applied during orthodontic tooth movement (OTM). As a result, orthodontic treatments may take longer than necessary, leading to unwanted side effects. This review aimed to identify an optimal force range with the rate of OTM as the primary outcome. External apical root resorption and pain were evaluated as secondary outcomes, and the influence of growth was examined. Five electronic databases were searched (MEDLINE via PubMed, Embase via OVID, Cochrane Library, CINAHL, and Web of Science) with no publication date or language restrictions. Inclusion eligibility screening, quality assessment, and data extraction were performed by 3 investigators. Each retrieved record was assessed by 2 observers independently. Only randomized controlled trials and randomized split-mouth studies were included. A total of 12 articles satisfied the inclusion criteria—two randomized controlled trials and 10 randomized split-mouth studies. Only 1 study showed a low risk of bias, whereas the remaining 11 were unclear. The qualitative analysis showed that forces between 50 cN and 250 cN produced a similar OTM rate; forces >250 cN yielded a slightly higher rate but were accompanied by adverse effects. Because of considerable heterogeneity in methodology, clinical diversity with varying forces between 18 cN and 360 cN, and poor statistical reporting, a meta-analysis was deemed inappropriate. Forces between 50 cN and 100 cN seem optimal for OTM, patient comfort and potentially exhibit fewer side effects. Nevertheless, careful data interpretation is necessary because of the lack of strong evidence. Protocol registration: PROSPERO CRD42016039985. •Two randomized controlled trials and 10 randomized split-mouth studies were assessed in this systematic review.•Risk of bias was low in 1 study, unclear in 11.•Forces of 50 cN-100 cN seem optimal for orthodontic tooth movement, patient comfort, and potentially exhibit fewer side effects.•Due to considerable heterogeneity in methodology, clinical diversity with varying forces between 18 cN-360 cN and poor statistical reporting, a meta-analysis was deemed inappropriate.