Context: Patients with acute myeloid leukemia (AML) in RCTs may not reflect the population seen in clinical practice due to strict eligibility criteria. Objective: To evaluate outcomes in clinical practice with IC vs venetoclax-containing regimens based on the VIALE-A trial eligibility criteria in patients with AML from the Connect® Myeloid Disease Registry (NCT01688011). Design: Patients were stratified into 3 groups: 1) eligible: met all VIALE-A inclusion criteria; 2) unfit: ineligible for VIALE-A; 3) fit: ineligible for a venetoclax-based regimen in VIALE-A (would have qualified for IC). Baseline characteristics were summarized by group. Induction regimens included IC or venetoclax-based therapies. Main Outcome Measures: OS was estimated by Kaplan–Meier method. Hazard ratios (HR) for induction regimens were estimated using Cox models adjusted for age, ELN risk, ECOG, frailty score, and comorbidity index. Results: Of 734 patients (Dec 2021), 61% were male; 84% were white; median age 71 years. Only 26% of patients (n=192) were eligible for VIALE-A; 45% (n=327) and 29% (n=215) were ineligible due to unfitness and overall fitness, respectively. The main reason for VIALE-A ineligibility was high overall comorbidity grade (n=265 [36%]). At baseline, fit patients intended to undergo transplant more often than unfit patients. Median OS (mOS) for eligible, unfit, and fit patients was 14, 10, and 22 months, respectively (HR [95%CI], eligible vs unfit, 1.02 [0.83–1.25], P-value, NS; eligible vs fit, 1.77 [1.38–2.25], P<0.0001; unfit vs fit, 1.74 [1.40–2.16], P<0.0001). Unfit patients receiving IC had significantly longer mOS (14 vs 6 months, respectively; HR, 0.51 [95%CI, 0.27–0.98]; P=0.042) and were more likely to receive a transplant (16% [n=17] vs 1% [n=1], respectively) vs those receiving venetoclax-based regimens. Eligible patients receiving IC (n=31) tended to have shorter mOS (13 months) vs patients receiving venetoclax-based therapies (n=27; 23 months; HR, 1.45 [95%CI, 0.66–3.17]; P-value, NS). Conclusions: Most patients with ND AML in the Connect® Myeloid Disease Registry would have been ineligible for VIALE-A due to being too fit or unfit. Among patients ineligible for an RCT due to unfitness, there was an association with increased OS in patients receiving IC vs those receiving venetoclax-based therapies.