Background: Advanced care planning (ACP) allows patients to express preferences for medical treatment toward the end of life. Reduced healthcare resource utilization has been observed with ACP. The association of ACP and hospitalization was assessed among patients who initiated second line (2L) therapy for metastatic non-small cell lung cancer (mNSCLC). Methods: Adults who received 2L treatment for mNSCLC were identified in a retrospective study of claims from Humana Medicare Advantage, following its launch of ACP programs in 2015. In this cohort, patients who participated in ACP programs and patients who did not were matched 2:1 by age, sex, race, population density of residence, and year of 2L termination. Categories of 2L therapy were chemotherapy, immuno-oncology (IO), and targeted therapy. Extent of comorbidity was assessed using the Deyo-Charlson Comorbidity Index (DCCI). The odds of hospitalization in the 12 months following initiation of 2L therapy for patients who participated in ACP programs and patients who did not were assessed with a logistic regression model, offset for patient months of follow-up, and considering therapy category and DCCI. Results: Ninety-eight patients who participated in ACP programs were matched to 196 patients who did not. More than half the cohort was male; median age was 71. There was no difference in therapy category or DCCI by ACP program participation. A greater proportion of patients with no ACP were hospitalized post-2L treatment, 57.7% vs 42.9%, P< 0.001. ACP was associated with a 52.1% decreased odds of hospitalization. Patients treated with IO or targeted therapy had reduced odds of hospitalization, 54.8% and 75.4% respectively, relative to patients treated with chemotherapy. Conclusions: This early assessment of ACP programs in patients with mNSCLC suggests ACP program participants may have fewer hospitalizations near the end of life. Possibly, ACP program participation presents opportunities for staff to identify changes in health status and prevent escalation to hospitalization. Also, because of its potential to reduce hospitalizations, selection of therapy should be considered as a part of ACP.