This study aimed to evaluate the association between muscle mass and vulnerability in institutionalized older adults. A cross-sectional study was carried out in eight philanthropic Long-Term Care Facilities (LTCF) located in the metropolitan area of Natal, Rio Grande do Norte, Brazil. The participants were individuals aged 60 years or older who were present in the institutions at the time of data collection. To assess muscle mass, the calf circumference was categorized into loss of muscle mass (<31 cm) and preserved muscle mass (≥31 cm). The vulnerability was assessed by The Vulnerable Elders Survey (VES-13). Of the 250 older adults evaluated, 46.1% presented loss of muscle mass, which was associated with the presence of physical limitation, vulnerability, and age group (p < 0.05). The presence of vulnerability was the main factor contributing to loss of muscle mass (R2 = 8.8%; B = 0.781; 95% CI 0.690–0.884; p < 0.001). Loss of muscle mass is associated with disability in institutionalized older adults.