Aim: To investigate the association between chronic opioid prescribing (COP) and cardiovascular disease (CVD) hospital admissions, utilising a retrospective cohort approach and linked dataset analysis. Methods: This retrospective cohort study analysed data from 24,260 adults aged 40 years and older, residing in the NHS Fife and NHS Tayside Health Board areas of Scotland, covering the years 2015 to 2021. COP participants were matched with unexposed controls. Statistical analysis included calculation of adjusted odds ratios (OR) to determine risk associations, alongside evaluation of potential pathways such as oxidative stress, endothelial dysfunction, and inflammation. Results: COP was associated with a greater than threefold increase in CVD hospital admissions (adjusted OR: 3.55, 95% CI 2.54–4.97). COP participants exhibited higher prevalence of risk factors, including elevated serum triglycerides, comorbid diabetes, and polypharmacy. Mechanisms such as oxidative stress, endothelial dysfunction, and inflammation were identified as potential pathways linking chronic opioid exposure to CVD. Conclusion: Chronic opioid prescribing significantly increases the risk of cardiovascular hospital admissions. Targeted harm reduction strategies and screening interventions are essential to mitigate CVD risk among long-term opioid users. Future research should focus on the influence of opioid type, dose, duration of exposure, and multimorbidity on CVD outcomes in COP populations.