Background: The present study aimed at assessing the validity of self-reported drug use in people aged 35 and older in a pilot phase of a population-based cohort study. Methods: A total of 1038 adults over 35 years old in Khamene city in East Azerbaijan province were recruited for the pilot phase of Azar cohort; a province-level of a nationwide PERSIAN cohort study completing a questionnaire and providing biological samples from October to December 2014. Information about the history and duration of smoking tobacco, using drug and medication were obtained by the physician. The validity of the drug use was assessed through comparing the questionnaire response with three urine strip tests for the detection of morphine, amphetamine and methamphetamine among 259 randomly selected subjects. Results: The prevalence of drug use according to self-report was 2.6% (95% CI: 1.7%-3.8%).One-step drug test as the gold standard for the use of drug self-reported demonstrated a sensitivity(95% CI) and specificity 15% (10-22) and 99.7% (98.9%-99.9%) respectively. All participants with positive self-report were male; however, in the urine analysis drug test, it was positive for 7out of 68 randomly selected women. Conclusion: The validity of self-reported drug use in this population was low; therefore, the self reported use of the drug should be used with caution in this population. It is recommended to use alternative techniques to improve the validity of data using the self-report procedure.