BACKGROUND: We have assessed the role of stress on compliance of patients with diabetes mellitus (DM) and hypertension (HTN) with taking prescribed medications and following dietary and exercise regimens. METHODS: A total of 9544 individuals more than 19 years of age were selected from three counties in central Iran. The presence of DM and HTN were asked from participants. We defined treatment adherence (compliance) based on agreement of individual’s self-report behavior with recommendations from a physician. RESULTS: Awareness about DM and HTN was 82.6% and 49.9%, respectively. Multivariate analysis showed that odds ratio (OR) of high to low stress level was lower than one for both “usage of medication” and “following exercise regimen” in diabetics even after adjustment for either “age and sex” or “age, sex and education”. In hypertensive patients, OR of high to low stress level was lower than one for “usage of medication” even after adjustment for either “age and sex” or “age, sex and education” and also lower than one for “following exercise regimen” only as crude index. CONCLUSION: Cases with higher stress level had lower compliance for accepting either medication or exercise as a treatment option for their DM or HTN.