We assessed the concomitant impact of cigarette smoking and alcohol consumption in men presenting for primary couple's infertility. Data from 189 infertile men were analyzed. Semen analysis, serum hormones, and sperm DNA fragmentation (SDF) were obtained. Smoking status was categorized as follows: current nonsmoker (-S), moderate smoker (+MS), and heavy smoker (+HS). Alcohol consumption was categorized as follows: abstainer (-D), moderate drinker (+MD), and heavy drinker (+HD). Descriptive statistics and logistic regression models were applied. Among all the participants, 132 (69.8%), 30 (15.9%), and 27 (14.3%) patients were -S, +MS, and +HS, respectively. In addition, 67 (35.4%), 77 (40.7%) and 45 (23.8%) men were -D, +MD and +HD, respectively. Regarding concomitant habits, 52 (27.5%) patients were nonsmokers and abstainers (-S/-D: Group 1), 91 (48.1%) had at least one recreational habit (-S/+D or +S/-D: Group 2), and 46 (24.3%) were both smokers and drinkers (+S/+D: Group 3). Sperm concentration and progressive motility were lower in +HS and +HD, compared with -S and -D (all P <0.05), respectively. Similarly, both parameters were significantly lower in Group 3 than Groups 1 and 2 (all P <0.05). SDF values were higher in Group 3 than Groups 1 and 2 (both P <0.05). In multivariate analysis, follicle-stimulating hormone (FSH) levels and concomitant +S/+D status were independent predictors of impaired sperm concentration and progressive motility (all P <0.05). Heavy smoking and heavy drinking were associated with worse seminal parameters than moderate smoking/drinking and nonsmoking/abstaining. When concomitant, +S/+D status has an even greater detrimental effect on semen parameters.