Frailty is associated with a pro-inflammatory state, which has been characterized by elevated levels of systemic inflammatory biomarkers, but has not been related to the number of co-existing chronic diseases associated with inflammation. We sought to determine the extent to which a higher number of inflammatory-related diseases is associated with frailty and to identify the most common disease patterns associated with being frail in older adults. We performed binomial regression analyses to assess whether a higher count of inflammatory-related diseases increases the probability of frailty using data from the WHAS I and II, companion cohorts composed of 70-79-year-old community-dwelling older women in Baltimore, Maryland (n=620). An increase of one inflammatory-related disease was associated log-linearly with frailty (Prevalence Ratio (PR)=2.28, 95% Confidence Interval (CI)=1.81-2.87). After adjusting for age, race, education, and smoking status, the probability of frailty remained significant (PR=1.97, 95%CI=1.52-2.55). In the frail population, chronic kidney disease (CKD) and depressive symptoms (Prevalence=22.9%, 95%CI=14.2-34.8%); CVD and depressive symptoms (21.7%, 95%CI=13.2-33.5%); CKD and anemia (18.7%, 95%CI=11.1-29.7%); cardiovascular disease (CVD), CKD, and pulmonary disease (10.7%, 95%CI=5.2-21.0%); CKD, anemia, and depressive symptoms (8.7%, 95%CI=3.9-18.2%); and CVD, anemia, pulmonary disease, and depressive symptoms (5.0%, 95%CI=1.6-14.4%) were among the most frequent disease combinations. Their prevalence percentages were significantly higher in the frail versus non-frail women. A higher inflammatory-related disease count, perhaps reflecting a greater pro-inflammatory burden, increases the likelihood of frailty. Shared mechanisms among specific disease combinations may further contribute to this risk.