ObjectivesThe current study aimed to examine the association between the number of medications, polypharmacy, and frailty in community-dwelling older adults. In addition, the cutoff score for the number of medications related with frailty in this sample was determined.MethodsA cross-sectional analysis was performed using data of 328 individual aged between 65 and 85 years from the Midlife in the United States (MIDUS 2): Biomarker Project, 2004–2009, a multisite longitudinal study, for 328 individuals aged between 65 and 85 years. All the participants were categorized into two groups based on the number of medications used: no polypharmacy (n= 206) and polypharmacy (n= 122). The polypharmacy was defined as having 5 or more medication per day. Frailty status was measured using a modified form of Fried frailty phenotype through the presences of the following indicators include low physical activity; exhaustion; weight loss; slow gait speed and muscle weakness. Participants were categorized into three different groups based on total score: 0 as robust, 1 to 2 as prefrail, 3 or more as frail. The relationship between no. of medications, polypharmacy, and frailty was examined using a multinomial logistic regression model. The model was adjusted for age, sex, BMI, and no. of chronic conditions. Receiver operator characteristics and area under the curve were used to determine the cutoff number of medications.ResultsNumber of medications, and polypharmacy were associated with being frail (relative risk ratio [RRR]: 1.30; 95% confidence interval [CI]: [1.12, 1.50],p= 0.001), (RRR: 4.77; 95% CI [1.69, 13.4],p= 0.003), respectively. Number of medications with cutoff 6 medication or more was associated with being in frail category with sensitivity of 62% and specificity of 73%.ConclusionPolypharmacy was shown to be significantly related to frailty. A cutoff score of 6 or more medications distinguished frail from non-frail. Addressing polypharmacy in the older population might ameliorate the impact of physical frailty.