OBJECTIVES: This study aims to assess the profile and predictors of Health-Related Quality of Life (HRQoL) in Type II Diabetes Mellitus (T2DM) patients of Quetta, Pakistan. METHODS: The study was designed as a questionnaire based, cross sectional analysis. 300 Type II diabetic patients attending public and private hospitals were targeted for data collection. In addition to demographic and disease related information, Euroqol Quality of Life was used to measure HRQoL. Moreover, Drug Attitude Inventory and Michigan Diabetes Knowledge Test were used to assess medication adherence and diabetes related knowledge respectively. Treatment satisfaction was assessed by patient’s experience towards health care professionals and available facilities. Descriptive statistics were used to elaborate patients’ demographic and disease related characteristics. Binary logistic regression was used to predict factors independently associated with HRQoL. SPSS v. 20 was used for data analysis and p < 0.05 was taken as significant. RESULTS: Patients in the current study reported poor HRQoL with mean score of 0.48 ± 0.36. Age, duration of disease, number of prescribed drugs, medication adherence and treatment satisfaction were significantly associated (p<0.05) with HRQoL in the cross tabulation analysis. The significant variables were entered into the model that showed significant goodness of fit with highly significant Omnibus Test of Model Coefficient (Chi-square =12.983, p = 0.030, df = 4). Medication adherence was reported as a significant predictor of HRQoL with an increase of one adherence score was associated with improvement of HRQoL by a factor of 1.75 provided other variables remain constant. CONCLUSIONS:  The study presents a model that is associated with HRQoL of patient with T2DM, where medication adherence shaped as a predictor of HRQoL. Healthcare professionals should pay special attention on patients’ medication taking behaviour and should put their efforts in explaining the benefits of the medication adherence to the patients