Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Tobacco use entails, during pregnancy, a serious risk to the mother and harmful effects on the development of the child. Europa has the highest tobacco smoking prevalence (19.3%) as compared to a worldwide mean of 6.8%. Twenty to thirty percent of pregnant women used tobacco during pregnancy worldwide. These data emphasize the urgent need for community education and implementation of prevention strategies focused on risks associated to tobacco use during pregnancy. Objective: The aim of this study is to investigate the efficacy of an intervention that incorporate a serious game (Tobbstop) to help pregnant smokers to quit smoking. Methods: A two-arm randomized controlled trial enrols 42 pregnant women who were visited in two primary care centres in Catalonia, Spain, between March 2015 and November 2016. All participants were pregnant smokers, over the age of 18 years, attending consultation to a midwife during the first trimester of pregnancy who expressed their desire to stop smoking. Participants were randomized to intervention (n= 21) or to control group (n = 21). Intervention group were instructed to install the game on their smartphone or tablet and use it for 3 months. Until the delivery, all participants were assessed about their stage on smoke cessation during their follow-up midwife consultations. The primary outcome was continuous tobacco abstinence until delivery confirmed by amount of CO at each visit, measured with a carboxymeter. Results: Continuous abstinence until delivery outcome was 57.1% (12/21) in intervention group and 14.3% (3/21) in control group (Hazard Ratio (HR) = 4.31; 95% CI, 1.87-9.97; P = 0.001). Mean of total days without smoking until delivery was higher in intervention group (mean 139.75; SD 21.76) than control group (mean 33.28; SD 13.27; P <.001). Kapplan-Meier survival analysis showed that intervention group has a higher abstinence rate compared with control group (log-rank test, X2 13.91; P <.001). Conclusions: Serious game’s use is associated with an increased likelihood to maintain abstinent during the intervention period compared with those not using the game. Pregnancy is an ideal opportunity to intervene and control tobacco use among future mothers. On the other hand, serious games is an emerging technology, growing in importance, which is shown as a good tool to assist in maintaining women without smoking and help behaviour change during pregnancy. However, due to study design limitations, these outcomes should be interpreted with caution. More research, using larger samples and longer follow-up periods, is needed to replicate the findings of this study. Clinical Trial: Trial Registration: ClinicalTrials.gov NCT01734421; https://clinicaltrials.gov/ct2/show/NCT01734421 (Archived by WebCite at http://www.webcitation.org/75ISc59pB)