The effects of passive smoking on asthma are well documented, however there is limited research conducted to study the relationship of asthma and smoking among adult populations. This article aims to investigate the gender differences when studying the relationship of asthma prevalence and smoking and further explore if rural/urban living affects the relationship over time. The longitudinal National Population Health Survey (NPHS) dataset was used. For analytic purposes five time periods were used. Generalized estimating equation (GEE) approach was used to obtain the odds ratios and 95% confidence intervals. A total of 11,223 participants ranging in age from 18 to 64; 5,382 men and 5,841 women, were included in the baseline time point (1994-1995). Rural/urban living for the present analysis was an effect modifier for the relationship of asthma prevalence and smoking, and this was true only for women. The results showed that female smokers and ex-smokers residing in rural locations were 1.4 times (95% CI: Rural Smokers = 1.02-1.94, and Rural Ex-smokers = 1.02-2.02) more likely to be diagnosed with asthma compared to non-smoking urban women. Results indicate that the combination of living in a rural area and smoking increases the risk of asthma prevalence among women but not among men.