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Introduction Fluoroquinolone (FQ) antibiotics have been linked to tendon disorders, particularly Achilles rupture (AR), leading to prescribing caution. This study examined whether FQ exposure is associated with an increased risk of AR using real-world electronic health records.Materials and Methods A retrospective cohort analysis was performed using the a Global Collaborative Network (TriNetX), incorporating data from 162 healthcare organisations. Adults (≥18 years) prescribed a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, delafloxacin, gemifloxacin, norfloxacin) were compared with those prescribed aminopenicillins or cephalosporins (e.g. amoxicillin, ampicillin, cephalexin, cefuroxime, penicillin G/V). Outcomes: diagnosis or repair of AR were analysed from 1 to 1095 days post-prescription. Propensity score matching (1:1) adjusted for demographics.Results Before matching, 5.15 million FQ and 21.89 million comparator prescriptions were identified. After matching, both cohorts contained 4,650,221 patients (total 9.3 million). Within 3 years, AR occurred in 1,221 (FQ) vs 2,203 (comparator). FQ exposure was not associated with higher risk (risk ratio 0.554, 95% CI 0.517–0.594) and showed a hazard ratio 0.603 (95% CI 0.562–0.646; p = 0.014). Kaplan–Meier survival was similar between cohorts (99.95% vs 99.92%).Conclusion In this large, propensity-matched analysis of 9.3 million patients, fluoroquinolone antibiotics were not associated with an increased risk of Achilles rupture. Our findings challenge the presumed causal relationship and may reassure clinicians when fluoroquinolones are clinically indicated.