Substance abuse in the workplace has been a growing concern in recent years and ways to detect employees and applicants who use drugs has been the subject of much debate. Aims of this research are; to estimate the prevalence rate of drug dependence among a sector of at risk group of industrial workers at four different worksites in Alexandria, and to identify the socio-demographic and psychological profile of drug dependent workers. The work aims as well at, investigating the relationship between workers drug dependence and some negative physical health and workplace outcomes, and testing the validity of personality testing in prediction of drug dependents. A cross-sectional comparative study was conducted in four large-seized establishments representing four industrial activities in Alexandria namely: metallurgic, pharmaceutical, petroleum and heavy transport. Study sample was 1200 employees equally allocated on the chosen four establishments. Research participants were subjected to physical and psychiatric examination, and structured interview where issues such as substance abuse behavior and some negative health and occupational outcomes were addressed. In addition workers job records were reviewed for work performance, labor turn over and absenteeism. Personality profile of participants was assessed using The Arabic Versions of Minnesota Multiphasic Personality Inventory [MMPI]-psychopathic personality subscale and Eyzenk Personality Inventory [EPI]. Urine drug screening using the Enzyme Multiplied Immunoassay Technique [EMIT] was repeated three times at random. Findings revealed that the overall prevalence rate of drug dependence among workers was 4.4%. The commonest drug abused was cannabis [1.3%], followed by alcohol [1.0%]. The metallurgic establishment recorded the highest rate of drug dependence [5.68%], followed by heavy transport drivers [4.67%]. Drug dependence was significantly associated with some adverse health and occupational outcomes mainly: cognitive and affective impairment, absenteeism, decreased work performance, labor turn over and work accidents. The psychopathic scale of MMPI proved to have high accuracy in prediction of drug dependence among workers. Workplace drug prevention programs should include not only, a policy, drug testing and access to treatment and rehabilitation services but also, education and training of employees.