ABSTRACT Background: Initial evidence suggests a role for Google Trends (GT) in monitoring use and interest in Electronic Nicotine Delivery Systems (ENDS). Objective: To examine the validity of GT data for assessing population behavior and interest in ENDS. Methods: GT search, done from the US and India to assess: (a) whether descriptive and statistical trends of specific search words depicting online interest in ENDS were similar to the published reports on actual use of these products in the US; (b) correlations between state-wise relative search volumes (RSV) of these words and prevalence of ENDS use; (c) the change in the online interest of ENDS after change in its regulatory policy. Results: Locally weighted scatter plot analysis showed “electronic cigarette,” “vaping,” and “cigarette” trends mirrored the use trend reported by the US-based National Youth Tobacco Survey (2019). Online interest in “Juul pods” followed the trends of its use. Geo-spatial RSVs of “electronic cigarette” (r=0.74, p<0.0001) and “vaping” (r=0.55, p<0.0001) correlated positively with state-wise prevalence of switch to ENDS in adults. Complete ENDS use prohibition in India was associated with a decrease in the online interest in “electronic cigarettes” (t=3.18, p=0.01) and “vaping” (t=2.3, p=0.04). Regulation of use in New Mexico (USA) was associated with a reduction in “electronic cigarettes” (t=4.09, p=0.0005) but not in “vaping.” Conclusion: GT may be used to validate existing information and assess the potential effect of ENDS regulations. Its role can also be extended for monitoring interest and use of other drugs and alcohol.