Background:Precise assessment of the prevalence of illicit drug use, face various methodological challenges.Objectives:The current study aimed to investigate the prevalence of illicit drug use among students studying at Universities in Shahroud (Northeast of Iran) through crosswise method.Patients and Methods:Participants of this cross-sectional study were 1646 students at Universities in Shahroud. The data collection instrument was a questionnaire designed based on crosswise model (CM).Results:The results of the study showed that 19% of students used at least one kind of illicit drug and 14.9% used opium residue once in their life. Moreover, 3.5% of students used drug and 3% used opium residue during the last month; 40.3% of the students admitted that they fully understood the instruction of the questionnaire; 9.6% said that did not comprehend the instruction at all, and 38.1% believed they partly understood the instruction. The result showed that 33.7% of the students fully trusted, 39.8% partly trusted, and 18.4% poorly trusted this method. There was a significant relationship between comprehension level and trust in CM (P < 0.001).Conclusions:This method can be appropriate to estimate sensitive issues; however, lack of understanding the method or doubting the confidentiality of the responses can lead to bias in the results. That is to say, if the instructions are introduced better, the level of trusting the method will increase and accordingly more reliable responses can be obtained. More studies under controlled conditions are required to interpret the findings of the current study better.