To examine the individual and combined associations of non-cardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF).We conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of non-cardiac conditions (<3 vs ≥3) and/or mobility impairment (defined by the use/nonuse of a wheelchair, cane, or walker), categorizing them into four subgroups. Outcomes included all-cause death and hospitalizations for HF or any cause.Among 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with <3 non-cardiac conditions/no mobility limitation, adjusted hazard ratios (HR) for all-cause death among those with <3 non-cardiac conditions/mobility limitation, ≥3 non-cardiac conditions/no mobility limitation, ≥3 non-cardiac conditions/mobility limitation (vs.) were 1.40 (95% CI, 1.31-1.51), 1.72 (95% CI, 1.69-1.75), and 1.93 (95% CI, 1.85-2.01), respectively. We did not observe an increased risk of any-cause or HF-related hospitalization related to the presence of mobility limitation among those with a greater burden of non-cardiac multimorbidity. Consistent findings regarding mortality were observed within groups defined according to age, gender, and HF type (preserved, reduced, mid-range ejection fraction), with the most prominent impact of mobility limitation in those <65 years of age.There is an additive association of mobility limitation, beyond the burden of non-cardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients.