PURPOSE: Poor patient experiences and increasing costs from undertreated symptoms require approaches that improve patient-reported outcomes and lower expenditures. We developed and evaluated the effect of a lay health worker (LHW)-led symptom screening intervention on satisfaction, self-reported overall and mental health, health care use, total costs, and survival. METHODS: From November 1, 2015, to September 30, 2016, we enrolled in this study all newly diagnosed Medicare Advantage enrollees with stage 3 or 4 solid tumors or hematologic malignancies who were receiving care in a community oncology practice. We evaluated symptom changes from baseline to 12 months for the intervention group. We compared with a control group (a historical cohort of Medicare Advantage enrollees diagnosed with cancer from November 1, 2014, to October 31, 2015) changes in satisfaction and overall and mental health with validated assessments at diagnosis and 5 months postdiagnosis, 12-month health care use, total costs, and survival. RESULTS: Among 186 patients in the intervention group and 102 in the control group, most were female and non-Hispanic white or Hispanic, and the mean age was 79 years. There were no survival differences between the groups. Relative to the control group, the intervention group experienced improvements in satisfaction with care (difference-in-difference: 1.35; 95% CI, 1.08 to 1.63), overall health (odds ratio, 2.23; 95% CI, 1.49 to 3.32), and mental or emotional health (odds ratio, 2.22; 95% CI, 1.46 to 3.38) over time; fewer hospitalizations (mean ± standard deviation: 0.72 ± 0.96 v 1.02 ± 1.44; P = .03) and emergency department visits per 1,000 members per year (0.61 ± 0.98 v 0.92 ± 1.53; P = .03), and lower median (interquartile range) total health care costs ($21,266 [$8,102-$47,900] v $31,946 [$15,754-$57,369]; P = .02). CONCLUSION: An LHW-led symptom screening intervention could be one solution to improve value-based cancer care.