Left ventricular (LV) assist devices (LVADs) are known to elicit reverse remodeling by mechanically unloading the left ventricle. Current guidelines target a reduction in LV end-diastolic diameter (LVEDD) of 15% compared with pre-LVAD dimensions; however, there is significant heterogeneity in the degree of unloading achieved. We sought to investigate factors associated with mechanical unloading at 6 months of LVAD support.Data were retrospectively collected for 75 LVAD recipients at five time points: pre-LVAD, within 14 days post-LVAD, and at 1, 3, and 6 months post-LVAD. The percentage change in LVEDD between the pre-LVAD and 6 months post-LVAD time points was termed ΔLVEDD. Optimal LV unloading was defined as ΔLVEDD of ≥15% at 6 months. Patients who achieved optimal unloading (group A, n = 30) were compared with patients who did not (group B, n = 45).At 6 months, optimally unloaded patients (group A) demonstrated higher fractional shortening (15% ± 10% vs 10% ± 7%, P = .007), lower rates of moderate or severe mitral regurgitation (10% vs 33%, P = .02), and lower pulmonary capillary wedge pressure (9 ± 4 vs 16 ± 7 mm Hg, P = .02). Right ventricular dysfunction was more prevalent at 6 months in poorly unloaded (group B) patients (73% vs 43%, P = .008). Between hospital discharge and 6 months, the percentage increase in pump speed (Δ revolutions per minute) was higher in group A patients (4.4% ± 3.7% vs 0.1% ± 2.6%, P < .001). In a multivariate analysis, Δ revolutions per minute and tricuspid annular systolic velocity (S') at 6 months were independently associated with 6-month ΔLVEDD.Recipients of LVADs who undergo progressive pump speed up-titration during outpatient follow-up are more likely to sustain optimal LV unloading. Progressive LVAD-related right ventricular failure is prevalent in suboptimally unloaded patients.