Background: Of the 14.3 million Mexicans who smoke, only a minority take advantage of evidence-based approaches to smoking cessation. Mobile health interventions have the potential to increase the reach of effective cessation interventions in Mexico. Objective: This study aimed to assess the feasibility and acceptability of an innovative, personalized, and interactive smoking cessation mobile intervention developed for Mexican smokers. Methods: We recruited 40 Mexican smokers to participate in Vive sin Tabaco... ¡Decídete!, a smoking cessation program that uses a tablet-based decision support software to drive a 12-week text messaging smoking cessation program and pharmacotherapy support. Outcome measures included participant text messaging interactivity with the program, participant satisfaction, and 12-week verified abstinence using urinary cotinine testing or exhaled carbon monoxide. Results: Average age of the participants was 36 years (SD 10.7), and they were primarily male (65%, 26/40) with at least an undergraduate degree (62%, 25/40). Most participants (95%, 38/40) smoked daily and were interested in quitting in the next 7 days. As an indicator of participant interactivity, participants sent an average of 21 text messages during the 12-week intervention (SD 17.62). Of the 843 messages that participants sent to the program, only 96 messages (11.3%, 96/843) used keywords. At 12 weeks, 40% (16/40) of participants were biochemically verified (87%, 35/40, follow-up rate). The majority of participants (85%, 30/35) reported being very satisfied or extremely satisfied with the program. Conclusions: The Vive sin Tabaco... ¡Decídete! smoking cessation mobile intervention was accepted by participants, generated high satisfaction and high text messaging interactivity, and resulted in a noteworthy cessation rate at the end of treatment. This intervention is a promising strategy for smoking cessation in Mexico. Additional testing as a formal randomized clinical trial appears warranted.