PURPOSE The purpose of the study was to measure the rate of non-compliance and the factors contributing to non-compliance among the diabetic patients in the Al Hasa region of Saudi Arabia. MATERIALS AND METHODS A cross-sectional survey was conducted in the Al Hasa region during the period of June 2010 to June 2011. Random sampling was carried out for the selection of 535 diabetic patients from three chronic disease centers in different parts of Al Hasa. The data were collected by means of interviewing questionnaires and file records. Any patient who had been prescribed optimum treatment and was properly advised on diet and exercise for his / her diabetes, but did not follow the medical advice, with Hb1AC of more than 7% at the time of interview, was considered as non-compliant. RESULTS The overall prevalence of therapeutic non-compliance of the participants was 67.9% (n = 318, 95% CI 63.59 - 72.02%). The non-compliance of males (69.34%) was higher than females (65.45%, P = .003). The non-compliance among the urban participants was significantly higher than (71.04 vs. 60.15%, P = .023) in the rural participants. There was a statistically significant difference in the prevalence rate of non-compliance among the participants with different levels of education. Factors found to be significantly associated with non-compliance on bi-variate analysis were: female gender (OR = 1.90, CI =1.32-4.57),level of education (Illiteracy) (OR = 5.27, CI = 4.63 - 7.19), urban population (OR =5.22, CI= 3.65 - 8.22), irregularity of the follow-up (OR = 8.41, CI = 4.90 - 11.92), non-adherence to drug prescription (OR = 4.55 , CI = 3.54 - 5.56), non-adherence to exercise regimen (OR = 5.55, CI = 4.2 6 - 6.), insulin (OR = 1.29, CI = .71 - 1.87), and insulin with oral Metformin (OR = 1.20, CI = .65 - 1.75). CONCLUSION The findings indicate that there is a high rate of non-compliance among the diabetes patients in the Al Hasa region of Saudi Arabia and there is a definite need for improvement in the healthcare system, health education, and training of diabetic patients.