Background: The CARG tox score can predict risk of chemotherapy-related tox in older adults with cancer. GAIN can reduce tox vs standard of care (SOC) among these patients (pts); GAIN’s impact across CARG risk groups is unknown. Methods: A secondary analysis of the GAIN randomized clinical trial (NCT02517034) of pts aged ≥65 (solid tumor diagnosis, starting a new chemotherapy) was performed. Pts were randomized 2:1 to receive GAIN vs SOC and were categorized into low (0-5), medium (6-9), and high (10-20) risk groups according to CARG score. The primary outcome was incidence of grade 3-5 tox. Chi-square/Fisher’s exact tests were used to compare outcomes (GAIN vs SOC, stratified by risk groups). Log-rank tests were used to compare 1-year survival across risk groups. Results: This analysis included 600 pts: 26.5% low risk, 45.2% medium risk, 28.3% high risk. Table shows pt/treatment characteristics. For pts with low/medium risk scores, GAIN demonstrated a 14.0% (95% CI 4.1%-23.9%) reduction in tox vs SOC (p = 0.006). No significant reduction in tox was observed among pts with high risk scores (p = 0.86). One-year survival (GAIN vs SOC) for each risk group was 73.6% vs 67.4% (low risk), 68.5% vs 64.5% (medium risk), and 57.3% vs 61.7% (high risk), respectively (log-rank p = 0.10). Conclusions: Older adults with low/medium, but not high, CARG risk scores benefit from GAIN. Additional strategies may be needed to improve outcomes for pts with high CARG risk scores. Clinical trial information: NCT02517034.