To determine the root causes of patient safety events in a high-volume intravitreal injection clinic and to assess the effect of interventions to reduce the rate of events. Quality improvement study. All cases of intravitreal injection in a designated injection clinic between January 1, 2016, and December 31,2019. The injection clinic model involved an injecting physician, who usually differed from a prescribing physician. The procedural injection area was also physically separate from the retina outpatient clinic. A root cause analysis was used to determine the factors that contributed to possible patient safety events in an institutional quality improvement project. Specific interventions were implemented to address each specific root cause. The rates of patient safety events (never events and near misses), whether associated with patient harm or not, were compared before and after the intervention. Frequency (%) of patient-safety-related intravitreal injection events before (January 1, 2016, to December 31, 2018) and after (January 1, 2019, to December 31, 2019) intervention. The root cause analysis included complex treatment plans that could be difficult to interpret, insufficient time to adequately review the designated treatment plans, and the risk of human error given the pace and volume of scheduled injections. Quality improvement strategies included revising the standardized treatment plan documentation template, scheduling block time for injecting physicians to review treatment plans within 24 hours of the injection clinic, and requiring agreement between dual, independent, site, and medication verifications of the treatment plan by the injecting physician and an allied health coordinator before site marking. The rate of events was 0.1% (28 in 27 400, or 9.3 events per year) before intervention and decreased to 0.01% (1 in 9375, or 1 event per year) after intervention (P= 0.01). Most events were classified as near misses, and there were no instances of patient harm. A high level of patient safety can be achieved in a complex, high-volume intravitreal injection practice by recognizing potential safety issues and root causes and implementing relevant quality improvements. Although most events were near misses and no patients were harmed, reducing near misses can reduce the likelihood of harm associated with never events.