Opioid prescriptions continue to carry significant short- and long-term systemic risks, even following ophthalmic surgery. The goal of this study was to identify any association of opioid prescription, following ophthalmic surgery, with post-operative hospitalization, opioid overdose, opioid dependence, and all cause mortality. Retrospective cross sectional analysis PARTICIPANTS: Patients undergoing an ophthalmic surgery in the OptumLabs Data Warehouse. We used deidentified administrative claims data from the OptumLabs Data Warehouse to create three cohorts of patients for analysis from January 1, 2016 through June 30, 2022. The first cohort consisted of one-to-one propensity score matched patients who had undergone ophthalmic surgery and had filled a prescription for an opioid and not filled a prescription for an opioid. The second cohort consisted of patients who were considered opioid naïve and had filled a prescription for an opioid, matched to patients who had not filled a prescription for an opioid. The last cohort consisted of opioid naïve patients matched across the following morphine milligram equivalents (MME) groups: <40, 41 - 80, and >80. Short- and long-term risks of hospitalization, opioid overdose, opioid dependency/abuse, and death were compared between the cohorts. We identified 1,577,692 patients who had undergone an ophthalmic surgery, with 312,580 (20%) filling an opioid prescription. Among all patients filling an opioid prescription following an ophthalmic surgery was associated with increased: mortality (Hazard Rate (HR) 1.28, 95% Confidence Interval (CI) 1.25 - 1.31, p < 0.001), hospitalization (HR 1.51, 95% CI 1.49 - 1.53, p < 0.001), opioid overdose (HR 7.31, 95% CI 6.20 - 8.61, p < 0.001) and opioid dependency (HR 13.05, 95% CI 11.48 - 14.84, p < 0.001), compared to no opioid prescription. Furthermore, we found that higher MME doses of opioids were associated with higher rates of mortality, hospitalization, and abuse/dependence. Patients who filled an opioid prescription following an ophthalmic surgery experienced higher rates of mortality, hospitalization, episodes of opioid overdose, and opioid dependence compared to patients who did not fill an opioid prescription.