Abstract INTRODUCTION Leptomeningeal disease (LMD) is an aggressive, late-stage complication of systemic cancers that maintains a poor prognosis with an average survival of 3-6 months. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for the delivery of intrathecal chemotherapy in the treatment of LMD. However, widespread use of OR has been limited by reports of complications, limited physicians trained in their use, and the stigma of brain surgery. Here, we assess survival and complication rates for patients who received intrathecal chemotherapy through OR for LMD treatment. METHODS After IRB approval, chart review of patients who received at least one administration of intrathecal chemotherapy through OR for LMD treatment between 2017- 2020 at Mayo Clinic in Phoenix, Arizona was conducted. Charts were reviewed for demographics, treatment type, complications, and outcomes. RESULTS A total of 10 patients were included. The median overall survival from date of first OR injection was 110.5 days (95% CI: 64 – not estimable). The median time to progression from the first injection was 55.5 days (95% CI: 45 – 753). A total of 82 OR injections were conducted for an average of approximately 8 injections per patient. Two patients (20%) experienced mild adverse events – grade 2 or lower by Common Terminology Criteria for Adverse Events with a single injection. The majority of injections involved no adverse events with the overall risk of any complication at 2.4%. None of the patients experienced infection, a commonly reported complication of OR use. CONCLUSIONS Our results support the inclusion of intrathecal chemotherapy via OR into the treatment paradigm in patients with leptomeningeal malignancies. This approach is feasible, safe, and median survival is comparable with data reported in published series. The overall complication rate in patients receiving intrathecal chemotherapy through OR is very low including the risk of infection.