We aimed to compare sociodemographic characteristics, smoking patterns, beliefs and perceptions, nicotine dependence, and psychological indicators between flavored waterpipe (WP) tobacco (FWT) and non-flavored WP tobacco (non-FWT) smokers in Iran. A cross-sectional study was conducted in 94 WP-serving venues surrounding Tehran and Ardabil metropolitans in Iran. Convenience sampling was applied to select 900 current WP smokers [508 (56%) FWT-only and 392 (44%) non-FWT-only smokers] aged 18 years and older. Multivariable logistic regression was used to examine the independent characteristics of FWT and non-FWT smokers. Compared to non-FWT smokers, FWT smokers were younger (adjusted odds ratio [AOR]=0.88, 95% confidence interval [CI]: 0.87-0.90) and more likely to have ≥ 1 sibling who smoked WP (AOR=1.54, 95% CI: 1.06-2.24), share WP with others (AOR=2.52, 95% CI: 1.68-3.77), report current cigarette smoking (AOR=2.05, 95% CI: 1.23-3.42), and report confidence in quitting at any time (AOR=3.64, 95% CI: 2.45-5.39). FWT smokers were less likely to have seen (AOR=0.40, 95% CI: 0.27-0.60) or read (AOR=0.44, 95% CI: 0.24-0.80) warning messages on WP tobacco packages relative to non-FTW smokers. The most common self-reported reason for smoking WP was entertainment for both groups, followed by stress relief for non-FWT smokers and the escape from loneliness for FWT smokers. FWT-only smokers differ from non-FWT-only smokers in several aspects including being younger, having more positive beliefs and perceptions regarding WP use, and having higher cigarette smoking prevalence. These findings will help in developing more effective and targeted policies and cessation interventions for WP smokers according to flavor type they use, especially in the Middle East.