Both during and after hospitalization, nutritional care with daily intake of oral nutritional supplements (ONS) improves health outcomes and decreases risk of mortality in malnourished older adults. In a post-hoc analysis of data from hospitalized older adults with malnutrition risk, we sought to determine whether consuming a specialized ONS (S-ONS) containing high protein and beta-hydroxy-beta-methylbutyrate (HMB) can also improve Quality of Life (QoL). We analyzed data from the NOURISH trial-a randomized, placebo-controlled, multi-center, double-blind study conducted in patients with congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. Patients received standard care+S-ONS or placebo beverage (target 2 servings/day) during hospitalization and for 90 days post-discharge. SF-36 and EQ-5D QoL outcomes were assessed at 0-, 30-, 60-, and 90-days post-discharge. To account for the missing QoL observations (27.7%) due to patient dropout, we used multiple imputation. Data represent differences between least squares mean (LSM) values with 95% Confidence Intervals for groups receiving S-ONS or placebo treatments. The study population consisted of 622 patients of mean age ±standard deviation: 77.9±8.4 years and of whom 52.1% were females. Patients consuming placebo had lower (worse) QoL domain scores than did those consuming S-ONS. Specifically for the SF-36 health domain scores, group differences (placebo vs S-ONS) in LSM were significant for the mental component summary at day 90 (-4.23 [-7.75,-0.71]; p=0.019), the domains of mental health at days 60 (-3.76 [-7.40,-0.12]; p=0.043) and 90 (-4.88 [-8.41,-1.34]; p=0.007), vitality at day 90 (-3.33 [-6.65,-0.01]; p=0.049) and social functioning at day 90 (-4.02 [-7.48,-0.55]; p=0.023). Compared to placebo, differences in LSM values for the SF-36 general health domain were significant with improvement in the S-ONS group at hospital discharge and beyond: day 0 (-2.72 [-5.33,-0.11]; p=0.041), day 30 (-3.08 [-6.09,-0.08]; p=0.044), day 60 (-3.95 [-7.13,-0.76]; p=0.015), and day 90 (-4.56 [-7.74,-1.38]; p=0.005). In hospitalized older adults with cardiopulmonary diseases and evidence of poor nutritional status, daily intake of S-ONS compared to placebo improved post-discharge QoL scores for mental health/cognition, vitality, social functioning, and general health. These QoL benefits complement survival benefits found in the original NOURISH trial analysis. NCT01626742.