Background: There is a growing evidence of abuse of tramadol in some African and West Asian countries considering large seizures of such preparations in North and West Africa especially in Egypt. Urine testing for drugs of abuse has become an integral weapon in the nation's war against drugs. A limitation inherent in all urine drug testing is the possibility of sample adulteration or substitution. Aim of study:  To detect qualitative and quantitative effects of five adulterants on positive urine samples for tramadol. Subject and Method(s): This study was conducted in Clinical Toxicology Laboratory in Sohag University Hospitals. The samples were tested for its integrity by checking PH, specific gravity and creatinine. The samples were tested by RIA then confirmed and quantified by HPLC. Results: Urine samples adulterated with vinegar, drano and liquid hand soap generated false negative results by immunoassay testing. HPLC confirmation showed decrease tramadol conc. below limit of quantification in urine samples adulterated with 40%vinegar and 40% drano. Conclusion: Some adulterants make it easy to produce false negative results and the specimen integrity testing is inadequate in detection of these adulterants.