Zoledronic acid is an approved FDA once yearly injection for the treatment of osteoporosis. Although it is widely prescribed in our institution (Hamad Medical Corporation) in Qatar, yet there is no available data covering the efficacy and safety profile in Qatar. This study aimed to determine the usefulness of Zoledronic acid 5 mg in the treatment of Osteoporosis regarding the change in BMD (primary end point) and B-CTX (secondary end pint) from baseline and evaluate the safety and tolerability of this medication by assessing the reported ADRs. This is a retrospective observational study, a total of 108 patients with confirmed diagnosis of Osteoporosis were identified, and received at least one dose of Zoledronic Acid 5 mg annual infusion for treatment of Osteoporosis, through Hamad Medical Corporation (HMC) during the study period between January 2009 and May 2011. Patient’s medical profile was reviewed for Bone Mineral Density (BMD), and for the bone turnover marker (B-CTX). Additionally, to identify the adverse drug reactions, the nurse’s records of IV admixture room, patients profile and drug information center were reviewed. Patients who received Zoledronic acid 5 mg annual infusion showed significant increase in BMD values for the lumbar spine at (L2-L4) after the first dose and the second dose as well by (6.63 and 20% and P values of 0.039 and 0.024 respectively), the values of lumbar spine at (L2) trend to be increased over the two years (% P>0.05). After the second dose, femoral neck and total hip BMD values tend to be decreased without reaching significant values. The biochemical markers were improved post-Zoledronic acid 5 mg annual dose by 17.9% and 10.9% (p values 0.161 and 0.14 respectively). A headache, flue-like symptoms, and fever were the most common adverse drug reaction associated with Zoledronic acid 5 mg IV administration. The once-yearly injection of Zoledronic acid 5 mg improves BMD at the lumbar spine, shows good tolerability and favorable safety profile. No evidence was found that the IV administration of Zoledronic acid 5 mg showed improvement in the BMD of femurs and bone turnover marker (B-CTX), or proves its association with severe ADR.