The escalating use of khat (Catha edulis) in East Africa and Arabia is a major concern for public health. Yet little is known about the impact of khat on behaviour. To that end, there has been no study in the region to assess the extent to which dependence syndrome is associated with khat use in this population. We examined in this study was psychometric properties of the Severity of Dependence Scale-Khat (SDS-khat), gender differences in patterns of khat use and dependence, and the extent to which age moderated the link between gender and khat dependence. Two-hundred and ninety-two khat chewers recruited in two Yemeni cities completed face-to-face interviews asking about demographics and patterns of khat use. Validity of SDS-khat was examined by the principle component analysis and reliability of the scale was tested by the Cronbach's alpha. A series of chi-square tests and analysis of variances (ANOVAs) were conducted to examine gender differences in khat use variables. The results indicated that the mean age of khat chewers was 30.52 years (95% CI: 29.34, 31.70) years, and 52% of them were males. The SDS-khat was found to have two factors with moderate reliability. This pattern was consistent when the analysis was conducted in the entire sample and in each gender. Male khat chewers reported more symptoms related to khat dependence than female chewers. A significant gender by age interaction in SDS-khat levels (p =0.013) revealed a positive association between age and khat dependence in women only. These results provide initial support for the use of SDS-khat in the assessment of khat dependence in Yemen. Gender differences in khat use patterns and dependence observed in this study call the need for more studies carefully examining the role of gender in khat research.