A prospective, controlled cohort study was started in 1998 to investigate the effects of orthodontic treatment in the early mixed dentition with the eruption guidance appliance. Occlusal changes were recorded in 167 treated children and 104 controls after they had reached the middle mixed-dentition stage. Treatment began when the first deciduous incisor was exfoliated (T1) and ended when all permanent incisors and first molars were fully erupted (T2). The children's mean ages were 5.1 years (SD 0.5) at T1 and 8.4 years (SD 0.5) at T2. From T1 to T2, overjet in the treatment group decreased from 3.1 to 1.9 mm and overbite from 3.2 to 2.1 mm. In the control group, overjet increased from 2.9 to 4.1 mm and overbite from 3.3 to 4.1 mm. At T2, the differences between the groups were highly significant (P <.001). At T1, 18% of the children in the treatment group and 22% of the controls had tooth-to-tooth contact between the maxillary and mandibular incisors. All others had an open bite, or the mandibular incisors were in contact with the palatal gingiva. At T2, tooth-to-tooth contact was observed in 99% of the treated children and 24% of the controls (P <.001). Almost half of children in both groups showed incisor crowding at T1. Good alignment of the incisors was observed in 98% of the treated children at T2, whereas maxillary crowding was found in 32% and mandibular crowding in 47% of the controls (P <.001). At T1, 41% of the children in the treatment group and 53% of the controls had a Class I relationship; the rest had either a unilateral or a bilateral Class II relationship. At T2, a Class I relationship was found in 90% of the treated children and 48% of the controls (P <.001). At least 1 occlusal deviation, including overjet > or =5 mm, overbite > or =5 mm, open bite, gingival contact of the mandibular incisors, crowding, or Class II relationship, was observed in 13% of the treated children, but the deviations were mild, and no child was considered to need treatment. In the control group, 88% of the children showed at least 1 occlusal deviation (P <.001). Treatment in the early mixed dentition with the eruption guidance appliance is an effective method to restore normal occlusion and eliminate the need for further orthodontic treatment. Only a few spontaneous corrective changes can be expected without active intervention.