To identify lifestyle-related determinants of hookah and cigarette smoking in Iranian adults, a total of 12,514 men and women aged >/=19 years in three counties in central Iran (Isfahan, Najafabad, Arak) were selected in multistage random sampling. Data on socio-demographic characteristics and lifestyle were collected in interviewer-administered questionnaires, as part of the baseline survey of the Isfahan Healthy Heart Program. Unhealthy lifestyle-related factors independently associated with cigarette and hookah smoking, were identified in sex-specific multivariate logistic regression analyses. High stress levels (OR: 1.55; 95% CI: 1.35-1.78 for men; OR: 1.63; 95% CI: 1.17-2.27 for women), family member smoking (OR: 1.61; 95% CI: 1.27-4.92 for men; OR: 2.49; 95% CI: 2.20-2.95 for women), and short/long sleep duration (OR: 1.18; 95% CI: 1.01-1.39 for men; OR: 1.52; 95% CI: 1.10-2.35 for women) were associated with cigarette smoking in both men and women. Poor diet was also related to cigarette smoking in men (OR: 1.55; 95% CI: 1.62-1.89). Family member smoking was associated with hookah smoking in both men (OR: 1.16; 95% CI: 1.05-3.12) and women (OR: 1.56; 95% CI: 1.02-4.92), and in addition high stress levels (OR: 2.87; 95% CI: 1.14-5.83) and short/long sleep duration (OR: 1.07; 95% CI: 1.02-2.41) were associated with hookah smoking in women. Unhealthy lifestyle-related factors co-occur with cigarette and hookah smoking in Iranian adults, likely increasing the risk for chronic health problems. Sex differences in the determinants of hookah and cigarette smoking may need to be taken into account in planning tobacco control strategies.