Objective: Research is needed to inform effective regulatory policy that can help curb electronic cigarette (e-cigarette) use among youth. However, several challenges interfere with studying e-cigarette use among youth. Social media may provide an outlet to overcome these challenges. Our objective was to provide instructional information on tested methods for using social media to study e-cigarette use among youth. Methods: We developed 13 advertisements that were used to recruit e-cigarette users 14-24 years old who lived in the United States. We measured the effectiveness of the advertisements and quality of the resulting data. Results: The advertisements reached 422,228 adolescents and young adults, 408 completed the survey, and 212 (52%) passed the quality check measures. The average cost per click was $0.36. Conclusions: Based on the current study, key recommendations for behavioral scientists interested in conducting e-cigarette research among youth include: (1) developing and testing multiple advertisements with the target audience; (2) advertising on social media platforms most commonly used by the target group; (3) tailoring (ie, age and interest) message options; and (4) using multiple types of data quality assurance items.