Introduction: Male infertility has increased during recent years in countries of the world including Iran. Among many factors that influence the infertility, smoking, alcohol, and addictive drugs were investigated in this study. Methods: This case-control retrospective study was conducted on 600 male patients consisting of 300 individuals with natural semen and 300 people with defective semen. The first step in investigation of infertility in each couple was to conduct a spermogram to detect the male infertility. The case group included men who referred to the Yazd Infertility Treatment Center and had at least one abnormal test result among considering the parameters of semen test. The control group included the men who referred to the same center and had normal semen test result. The data collection tools were a researcher-made checklist based on the parameters required for the study with epidemiological and observational design, as well as the semen analysis test.  Results: The age mean in the case and control groups were 34.71 and 33.82 years with the standard deviation of ± 7.3 and ± 6.41, respectively. The means of marriage age in the case and control groups were 26.28 and 26.28 ±5.3 years, respectively. The mean duration of infertility in the case group was 6.30 ± 4.60 and in the control group was 5.15± 3.88. No significant difference was observed between the mean age (P = 0.084) and marital age (P = 0.448) in two groups, but the mean duration of infertility (P <0.001) was significantly different between the two groups .The prevalence of smoking was significantly different between the two groups (P = 0.032). Considering the daily frequency of smoking, the highest rate was 11-20 cigarettes in both groups (case group 21.7% and control group 15.3%). The P value was set at 0.018. Conclusion: In this study, smoking and consumption of alcohol were not considered as the predictive factors of semen quality, but  consumption of drugs and the age of starting consumption of drugs had a significant relationship with the semen disorders.