OBJECTIVES:  Multimorbidity is highly prevalent among young adults and these adults often use multiple medication classes known as polypharmacy. Current definitions of polypharmacy are limited because they do not measure daily use of multiple medication classes. To examine the relationship between multimorbidity and polypharmacy. Polypharmacy was estimated with the commonly-used measure and a novel measure. METHODS:  In this cross-sectional study, data on fee-for-service Medicaid recipients (N = 54,907) were derived from 2010 Medicaid Analytic Extract files of Maryland and West Virginia. Nineteen chronic conditions based on the US Department of Health and Human Services framework were selected. Medication classes were identified using the National Drug Codes. Commonly-used polypharmacy measure was defined as number of drug classes (within an arbitrary 90-day time period) that was 1 standard deviation above the mean. The novel approach integrated the number of drug classes and duration of use to calculate simultaneous daily use medication classes. The simultaneous use of 5 or more different medication classes for a 60-day consecutive period was defined as polypharmacy. The association between multimorbidity and polypharmacy was examined with Chi-square tests and logistic regressions. RESULTS:  Polypharmacy was estimated at 17.1% under the commonly-used approach and 38.1% under the novel measure. Individuals with multimorbidity had higher rates of polypharmacy under both definitions (33.3% -commonly-used measure vs. 64.5% -novel measure). Adults with multimorbidity were more likely to have polypharmacy for both measures (AOR = 8.6, 95% CI =8.1 -9.2 -commonly-used measure; and AOR = 6.3, 95% CI =6.0 -6.5 -novel measure), compared to those without multimorbidity. CONCLUSIONS: Polypharmacy was highly prevalent among adults with multimorbidity regardless of the definition used, although the commonly-used definition may underestimate the rate of polypharmacy.