OBJECTIVES: The use of an Amharic version Simplified Medication Adherence Questionnaire in the assessment of medication adherence predictors among persons of Ethiopian descent. METHODS: A cross sectional study design was conducted using Audio-Computer Assisted Survey Interviewing system to evaluate factors that predict medication adherence among persons of Ethiopian descent. Patients were recruited from Ethiopian Communities. A patient had to be of Ethiopian descent and taking medications continuously to manage their condition. RESULTS: A total of 163 persons of Ethiopian descent with chronic diseases were recruited. The mean age of the participants was 56.6 years and the majority were female 54%. Of the 163 persons, 61.3%, were married and 95.7% were born in Ethiopia. About 58.9% resided in the District of Columbia followed by 23.9% in Virginia, and 10.4% in Maryland. The overall adherence level in this population was 34.4%. Findings from multivariable analysis showed that difficulty in communicating in English (p-value=0.018;OR=0.32), believing in holy water and spiritual healing (p-value=0.000;OR=8.63), high activity level (p-value=0.022;OR=4.18), following an unhealthy diet (p-value=0.029;OR=0.39), having a college degree (p-value=0.002;OR=0.14), and having graduate degree (p-value=0.020;OR=0.09) were statistically significant predictors of medication adherence adjusting for all other variables. CONCLUSIONS: Overall factors such as difficulty in communicating in English, believing in holy water and spiritual healing, high activity level, following an unhealthy diet, having a college degree and graduate degree were significant predictors of medication adherence adjusting for all other variables among persons of Ethiopian descent. These factors need to be taken into consideration when developing treatment plans for these patients. These findings will assist healthcare providers and researchers evaluate the level of non-adherence to medication among patients in this subgroup. Furthermore, identifying the significant predictors of medication adherence will provide guidance in the selection of future adherence intervention strategies for persons of Ethiopian descent.