Purpose: The purpose of this study was to investigate factors associated with drug misuse behaviors among polypharmacy elderly. Methods: This was a cross-sectional survey. Participants consisted of 116 polypharmacy elderly who were taking 5 or more medications each day. Data were collected via face to face interviews. Data were analyzed using the PASW 18.0 program. Data concerning predisposing factor (knowledge, benefit), enabling factor (communication with health care provider), and need factor (perceived health status, number of disease) were collected. Results: The total mean score of drug misuse behaviors among polypharmacy elderly was 3.04 out of 10 points. Communication with health care provider, perceived health status, and knowledge were found to be significantly correlated with drug misuse behaviors. In stepwise multiple regression analysis, a total of 42% of the variance in drug misuse behaviors was accounted for communication with health care provider, perceived health status, and knowledge. Conclusion: Therefore, education program for improving communication with health care provider, and knowledge should be designed and provided for polypharmacy elderly.