Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-Transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-Transplant ZA from days 100 to 365 post alloSCT was determined by a risk-Adapted algorithm based on serial bone density assessments and glucocorticoid exposure. Of 82 patients enrolled, 70 were alive and without relapse at day 100. A single pretransplant dose of ZA prevented femoral neck bone loss at day 100 compared with baseline (mean change '2.6±4.6%). Using the risk-Adapted protocol, 42 patients received ZA between days 100 and 365 post alloSCT, and this minimised bone loss at day 365 compared with pretransplant levels (mean change '2.9±5.3%). Femoral neck bone loss was significantly reduced in ZA-Treated patients compared with historical untreated controls at days 100 and 365. This study demonstrates that a single dose of ZA pre-AlloSCT prevents femoral neck bone loss at day 100 post alloSCT, and that a risk-Adapted algorithm is able to guide ZA administration from days 100 to 365 post transplant and minimise further bone loss.