Abstract This study investigated the association of substance use with daily hassles and coping strategies. The use of three classes of substances was investigated: psychotropic medications, illegal drugs, and alcohol. A representative sample of 300 Egyptian manufacturing workers was drawn. The average age of participants was 37.34 years (SD = 9.57). The results indicated that alcohol was used in the last month by 20% of the workers. Daily hassles and coping strategies are associated with substance use. However, coping strategies did not moderate the association. Positive coping strategies were associated with reduced likelihood of using substances, whereas negative coping strategies were associated positively with using substances. These findings point to the importance of addressing substance use in workers and suggesting strategies.