Abstract: Donor blood represents one of the most important sources of therapeutic preparations required for various cases necessitating transfusions of plasma or erythrocytes. While, thorough screening tests for, for example, syphilis and other infectious agents are conducted (as a routine test), other analytical tests aiming at the detection of drug residues are rare (if at all) performed. The present study was designed-as a preliminary study-to discover drugs of abuse in blood in donating King Abdul-Aziz Hospital (Makkah, Saudi Arabia). A total of 300 EDTA plasma samples (approximately 1.5 mL each) was obtained from a King Abdul-Aziz Hospital blood bank from voluntary blood donors after regular whole blood donation. Immediately after sampling, the plasma was separated in a centrifuge, transferred to a 2 mL Eppendorf tube and frozen until analysis. All donors were males; in the preliminary test, 28 cases (9.3%) were positive for one of screened substance (1 case; 0.3% were positive for amphetamine, 7 cases (2.3%) were positive for tricyclic antidepressants TCA and 20 cases (6.7%) were positive for tetrahydrocannabinol (THC). On the second screen, confirmed cases were 20 cases (6.7%), 1 case (0.3%) was positive for amphetamine, 2 cases (0.7%) were positive for TCA and 17 cases (5.7%). Positive cases were significantly younger than negative cases (25.80±2.58 vs. 27.34±3.08 years, respectively). The present study sheds light on the importance of screening blood and blood products in blood banks for commonly abused drugs, besides regular checkup for infectious diseases. It is advised to put this step as a routine in blood screening as much as the facilities permit to do so.