Allogeneic haemopoietic stem cell transplant (alloHSCT) patients are at increased risk of osteoporosis. Zoledronic acid (ZA) is a potent i.v. bisphosphonate; however, there are few data on ZA use after alloHSCT. The aim of this study is to examine the effect of a single 4 mg ZA infusion in alloHSCT patients with either osteoporosis (T-score < -2.5) or rapid bone loss post-alloHSCT. An uncontrolled, prospective study of 12 consecutive patients receiving ZA, predominantly within the first year post-HSCT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the spine and proximal femur pretransplant, pre-ZA and post-ZA. The median annualized percentage change in total hip BMD between the pretransplant scan and the scan immediately before ZA was -13% (range, -51 to +3.6%). After ZA treatment, the total hip BMD increased by a median of +3.3% (range, -20.4 to +14.8%) in 75% of patients. The median annualized percentage change in femoral neck BMD between the pretransplant scan and the scan immediately before ZA was -13.2% (range, -40 to +1.0%). Post-ZA, femoral neck BMD increased by a median of +1.4% (range, -22.2 to +33.6%). Only one patient continued to lose bone from the femoral neck post-ZA infusion. The median annualized percentage change in spinal BMD pretransplant was -12.5% (range, -38 to +6.9%). Post-ZA, spinal BMD decreased by a median of -2.8% (range, -27.6 to +24.4%). Four patients continued to lose bone from the spine post-ZA. ZA reduces bone loss in most patients after alloHSCT. Our data require confirmation in a larger prospective, randomized study.