Anchorage loss (AL) is a potential side effect of orthodontic mechanotherapy. In the present study, it is defined as the amount of mesial movement of the upper first permanent molar during premolar extraction space closure. In addition, AL is described as a multifactorial response in relation to the extraction site, appliance type, age, crowding, and overjet. For this study, 87 university clinic and private practice subjects, who were defined as maximum anchorage cases and had undergone bilateral maxillary premolar extractions, were divided into four groups according to extraction site (first vs second premolars), mechanics (lingual vs labial edgewise appliances), and age (adolescents vs adults). Overjet and crowding were examined from the overall sample. Data were collected from serial lateral cephalograms and dental casts. The results showed that as the severity of dental crowding increased, AL significantly decreased (r = -0.66, P = .001). Labial edgewise appliances demonstrated a significantly greater AL than did lingual edgewise appliances (1.15 +/- 2.06 mm, P < .05). A greater, though not statistically significant, AL was found in adults than in adolescents (0.73 +/- 1.43 mm). There was a slight nonsignificant increase in AL between maxillary second compared with first premolar extractions (0.51 +/- 1.33 mm). Overjet was weakly correlated to AL. These results suggest that AL is a multifactorial response and that the five examined factors can be divided into primary (crowding, mechanics) and secondary factors (age, extraction site, overjet), in declining order of importance.