ABSTRACT Objective This study investigates adverse drug event (ADE) reports from the FAERS related to FQs drugs (ciprofloxacin, levofloxacin, moxifloxacin, and ofloxacin) in patients aged 65 and older. The findings aim to guide the rational clinical use of these drugs in elderly patients. Methods We employed Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to analyze ADE reports for the representative FQ drugs from Q1 2015 to Q4 2023, covering 36 quarters. Results The analysis identified 6883 ADE cases for ciprofloxacin, 5866 for levofloxacin, 1498 for moxifloxacin, and 317 for ofloxacin. Moxifloxacin showed higher incidences of Cardiac disorders and Psychiatric disorders ADEs (4.01%, 23.11%).The strongly associated ADEs were Torsade de pointes(X2:255.69),Delirium(X2:4600.04),Dysphoria(X2:11802.38),Mental disorder(X2:3584.69);Vascular disorders ADEs were similar among FQs.Ciprofloxacin and levofloxacin showed higher ADE rates in musculoskeletal and connective tissue diseases (20.18% and 26.97%) compared to moxifloxacin(3.62%) and ofloxacin(9.25%),The most frequently reported and strongly associated ADEs were tendinitis (X2: 13383.57, X2: 31499.01), tendon pain (X2: 18730.22, X2: 40313.79), and tendon disorders (X2: 9534.69, X2: 13143.72).Additionally, moxifloxacin and ofloxacin showed higher ADE rates for eye disorders (10.61% and 15.03%). Significant ADEs included iridocyclitis (X2: 10931.34) and corneal erosion (X2: 1348.35). Conclusion Different FQs exhibit varying ADE profiles across cardiovascular, vascular and lymphatic, renal and urinary, psychiatric, musculoskeletal and connective tissue, and ocular systems. Patients with underlying systemic diseases should avoid FQs with higher ADE risks for their conditions. Enhanced monitoring and evaluation of FQs are crucial for promptly identifying and managing adverse reactions. Personalized medication plans for elderly patients should also be strengthened.