Background: Older people often take multiple medications. It is a policy priority to facilitate older people to stay at home longer. Three-quarters of nursing home placements in the US are preceded by a hospitalization. Objective: To investigate the association between polypharmacy and medication regimen complexity with hospital discharge destination among older people. Methods: This prospective cohort study comprised patients aged ≥70 years consecutively admitted to the Geriatric Evaluation and Management unit at a tertiary hospital in Adelaide, Australia, between October 2010 and December 2011. Medication regimen complexity at discharge was calculated using the 65-item validated Medication Regimen Complexity Index (MRCI). Unadjusted and adjusted relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for medication-related factors associated with discharge directly to home versus non-community settings (rehabilitation, transition care, and residential aged care). Results: From 163 eligible patients, 87 were discharged directly to home (mean age 84.6 years, standard deviation [SD] 6.9; mean MRCI 26.1, SD 9.7), while 76 were discharged to non-community settings (mean age 85.8 years, SD 5.8; mean MRCI 29.9, SD 13.2). After adjusting for age, sex, comorbidity, and activities of daily living, having a high medication regimen complexity (MRCI >35) was inversely associated with discharge directly to home (RR 0.39; 95 % CI 0.20-0.73), whereas polypharmacy (≥9 medications) was not significantly associated with discharge directly to home (RR 0.97; 95 % CI 0.53-1.58). Conclusion: Having high medication regimen complexity was inversely associated with discharge directly to home, while polypharmacy was not associated with discharge destination.