OBJECTIVES: This study sought to assess adherence to oral anti-diabetes mellitus medications and associated factors among clients reporting to four randomly selected Hospitals in the Volta region of Ghana. METHODS:  A cross-sectional study was conducted among type 2 diabetes mellitus clients who attended the Diabetes Clinic of four randomly selected Hospitals in the Volta region of Ghana between the months of January 2015 to March 2015. Adherence prevalence was assessed using the eight (8)-item Morisky Medication Adherence scale. Study participants were interviewed using a structure questionnaire to, among other things, determine the commonest self-reported reason (s) of non adherence. Data generated were analyzed using SPSS version 21. Cross-tabulation analysis was performed between the adherence levels and the indicators generated from the questionnaire. Multiple logistic regression was further performed between adherence level and the statistically significant variables. RESULTS: Adherence prevalence rate to oral anti-diabetes in Type 2 Diabetes Mellitus was found to be 47.75%.  In a multiple logistic regression analysis, the odds of adherence in respondents with fasting blood glucose of 1 – 6mmol/L (OR = 1.9, 95% CI 1.128 – 3.232, p-value 002) was about 2-fold the odds of having fasting blood glucose of above 10mmol/L while the odds of adherence among respondents with tertiary education was about 3-fold (OR=2.888, 95% CI 1.394 – 5.982, p-value 0.004) of those with no formal education. The commonest self-reported reason for non-adherence was forgetfulness. CONCLUSIONS: Adherence to oral anti-diabetes in type 2 diabetes mellitus was found to be suboptimal. Management of type 2 diabetes mellitus with oral anti-diabetes must include strategies to identify non-adherent clients for adherence counseling before modification of therapy in ensuring good glycaemic control and prevention of the more costly management of its complications.