BACKGROUND The authors compared the quality of life of patients with solid tumor neoplastic meningitis treated in a controlled trial that compared conventional intrathecal methotrexate with a depot cytosine arabinoside liposomal injection (DepoCyt). The authors evaluated the trade-off between toxicity and improved clinical outcome. METHODS Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis was used to evaluate data collected prospectively from a randomized clinical trial that compared DepoCyt with methotrexate. Sixty-one patients with confirmed solid tumor neoplastic meningitis were randomized to receive either methotrexate or DepoCyt. RESULTS Within the 12-month follow-up, the average patient in the DepoCyt arm (compared with the methotrexate arm) achieved 71 more days of neurologic progression-free survival and 52 more days of overall survival, but experienced slightly more days with toxicity. The DepoCyt regimen provided greater quality-adjusted survival regardless of the quality-of-life valuations placed on time with toxicity and time following disease progression (range, 44-79 days). This gain was significant (P < 0.05) for all patients except for those who placed a high relative value on time following disease progression. CONCLUSIONS The clinical benefits of DepoCyt offset a trend toward additional toxicity among patients with sold tumor neoplastic meningitis. The magnitude of the benefit depends on how the patient values time spent in toxicity and disease progression. The results of this analysis can be used at the bedside to make evidence-based individual treatment decisions.