Objective To evaluate the long⁃term efficacy of Zoledronic acid in the treatment of primary osteoporosis. Methods The medical records of 88 patients with primary osteoporosis，who had been injected with Zoledronic acid for more than 3 years at the General Hospital of the Southern Theater Command of the People′s Liberation Army from January 2011 to December 2021 were retrospectively analyzed.The data were collected and analyzed concerning bone mineral density（BMD）of lumbar spine L1⁃4，left femoral neck and left femoral neck upper end and bone turnover markers such as N⁃osteocalcin（N⁃OC），β⁃isomerized carboxy⁃telopeptide of type I collagen（β⁃CTX），parathyroid hormone（PTH）and procollagen type 1 N⁃peptide（P1NP）level at the baseline and medication within 1 ~ 6 years，new fractures during medication and adverse events. The efficacy of 6⁃year medica⁃ tion was evaluated. Results The average age of the patients was（64.94 ± 10.02）years，and the average duration of medication was（4.65 ± 1.07）years，the longest 6 years. The BMD of lumbar spine L1⁃4 and left femoral neck upper end was increased by 24.18% and 11.01% respectively compared with the baseline in the 6th year of treat⁃ ment. The BMD of the left femoral neck was increased to a largest extent against the baseline in the 5th year of treatment（+11.03%）. The BMD reached the peak of efficacy in the first 5 years of the medication，and then began to show a downward trend in the sixth year of medication（P < 0.001）. N ⁃OC，P1NP and other bone turnover markers all were declined significantly within 1 year of medication，but showed an upward trend after 3 years of medication. P1NP was 4.87% higher than the baseline at the 6th year of medication. A total of 5 cases of new frac⁃ tures during medication were found. No serious adverse reactions such as osteonecrosis of the mandible were found. Conclusion Zoledronic acid has the most significant effectiveness within 3 to 5 years of medication，and continued medication does no more good to the rise of BMD，indicating that suspension of the Zoledronic acid use can be considered after 5 years medication.