Severe osteogenesis imperfecta (OI) is a hereditary disorder characterized by increased bone fragility and progressive bone deformity. Cyclical pamidronate infusions improve clinical outcome in children older than 3 yr of age with severe OI. Because earlier treatment may have potential to prevent deformities and improve functional prognosis in young children, we studied nine severely affected OI patients under 2 yr of age (2.3–20.7 months at entry) for a period of 12 months. Pamidronate was administered iv in cycles of 3 consecutive days. Patients received four to eight cycles during the treatment period, with cumulative doses averaging 12.4 mg/kg. Clinical changes were evaluated regularly during treatment, and radiological changes were assessed after 6–12 months of treatment. The control group consisted of six age-matched, severely affected OI patients, who had not received pamidronate treatment. During treatment bone mineral density (BMD) increased between 86–227%. The deviation from normal, as indicated by the z-score, diminished from −6.5 ± 2.1 to− 3.0 ± 2.1 (P < 0.001). In the control group the BMD z-score worsened significantly. Vertebral coronal area increased in all treated patients (11.4 ± 3.4 to 14.9 ± 1.8 cm²; P < 0.001), but decreased in the untreated group (P < 0.05). In the treated patients, fracture rate was lower than in control patients (2.6 ± 2.5 vs. 6.3 ± 1.6 fractures/year; P < 0.01). No adverse side-effects were noted, apart from the well known acute phase reaction during the first infusion cycle. Pamidronate treatment in severely affected OI patients under 3 yr of age is safe, increases BMD, and decreases fracture rate.