The long-term effect of interventions that assist patients with establishing their end-of-life care preferences among patients with cancer remain relatively unknown. To evaluate the association of a long-term intervention of a lay health worker-led advance care planning intervention among patients with advanced stages of cancer with overall survival and end-of-life health care use and costs. This follow-up study of the EPAC randomized clinical trial conducted between August 2013 and February 2015 used data from 9.4 years after the first patient was enrolled with a data cut-off date of February 1, 2023. Overall, 213 participants with stage 3 or 4 or recurrent cancer in the US Veterans Affairs Palo Alto Health Care System were included. A 6-month lay health worker-led education and support intervention to assist patients with establishing their end-of-life preferences vs usual care. The outcomes of interest were overall survival, risk of death, restricted mean survival time, and palliative care, hospice, and acute care use in the final 30 days before death for participants who died. Among 213 participants randomized and included in the intention-to-treat analysis, the mean (SD) age was 69.3 (9.1) years; 211 (99.1%) were male, 2 (0.90%) were female. There were no demographic or clinical characteristic imbalances at enrollment. As of February 1, 2023, 188 had died. The intervention group had a 25% reduction in risk of death (hazard ratio, 0.75; 95% CI, 0.56-0.98); more palliative care (44 [50.0%] vs 35 [35.0%]) and hospice use (64 [72.7%] vs 53 [53.0%]); and lower emergency department use (20 [22.7%] vs 47 [47.0%]), hospitalizations (17 [19.3%] vs 46 [46.0%]), and median (IQR) total health care costs (median [IQR], $1637 [$383-$9026] vs $18 520 [$4790-$50 729]) than control group participants. The effects of the lay health worker-led intervention remain durable, with nearly complete follow-up, supporting integration into routine cancer care. ClinicalTrials.gov Identifier: NCT02966509.