Background: Meta-analyses of randomized controlled trials comparing atrial fibrillation (AF) ablation to medical therapy in patients with heart failure (HF) reported improvement in left ventricular ejection fraction (LVEF), quality of life using the Minnesota Living with HF Questionnaire (MLWHFQ), and 6-minute walk test (6MWT). Nonetheless, there was significant heterogeneity not accounted for suggesting that not all HF patients derive the same effect from AF ablation. Objectives: To evaluate if baseline LVEF or the etiology of the cardiomyopathy would moderate the efficacy of AF ablation. Methods: We performed random effects meta-regression using the mean baseline LVEF and total percentage of patients with non-ischemic cardiomyopathy (NICMP) in the placebo arms as moderator variables. Results: Seven trials with a total of 856 patients were included. The baseline LVEF in the control arm of trials ranged from 25% - 42.9%, and the percentage of patients with NICMP with in each trial varied from 35% to 100%. When baseline LVEF was used as the moderator variable, we observed no significant change in heterogeneity for any of the outcomes of interest (R2 0.00 – 0.02). However, when controlling for NICMP, heterogeneity dropped substantially for the outcomes of LVEF (I2 44.7%, R2 0.91), and MLWHFQ (I2 0.00%, R2 1.00) but not 6MWT (I2 67.4%, R2 0.00). This indicates that improvement in LVEF and MLWHFQ was greater in the AF ablation group when more patients with NICMP were included in the trials. Conclusions: In patients with systolic HF, AF ablation may be more beneficial in patients with NICMP.