Aim. The aim of this study is to analyze the etiological factors underlying the presence of maxillary midline diastema in a sample of orthodontic patients.Materials and Methods. One hundred patients who fulfill the inclusion criteria were selected from 1355 patients seeking orthodontic treatment. The pretreatment orthodontic records were analyzed. The width of the maxillary midline diastema was measured clinically with a digital caliper at two levels: the mesioincisal angles of the central incisors and five millimeters from the incisal edge. The two measurements were averaged, and patients with diastema of more than 0.5 millimeter in width were enrolled.Results. Diastema is a multifactorial clinical finding with more than one underlying etiological cause. The interrelationship between the familial pattern of midline diastema and the microdontia, macroglossia, labial frenum, and alveolar cleft conforms was clear. The effect of a mesiodens and the upper lateral incisor whether bilaterally missing, unerupted, or peg shaped was minimal.Conclusion. Etiological factors underlying maxillary midline diastema are interconnected. Using a checklist as a guide during handling maxillary midline diastema is important in the different stages of treatment.