Smoking cessation is a public health priority to reduce smoking-related morbidity and mortality. However, weight gain is a known primary reason for not trying to quit smoking. The aim of the current study was to investigate differences in weight gain associated with different pharmacological smoking cessation interventions. Randomized controlled trials (RCTs) that reported weight gain related to pharmacologic treatments for smoking cessation were analysed using network meta-analysis with a random effects model. Thirty-one RCTs with 5650 participants were included. Ten drugs and 22 regimens were identified. Nicotine patches plus fluoxetine, topiramate with/without nicotine patches, nicotine patches plus methylphenidate, nicotine spray/gum/lozenges, high-dose nicotine patches (42 mg/21 mg), naltrexone with/without nicotine patches, or bupropion with/without nicotine patches were associated with less weight gain than the placebo/control arm. Nicotine patches plus fluoxetine were associated with the least weight gain of all smoking cessation treatments. In addition, the nicotine patch plus topiramate and nicotine inhaler was associated with the best success rate and the least dropout rate, respectively. Overall, the nicotine patch 14 mg plus fluoxetine 40 mg, nicotine patch 14 mg plus fluoxetine 20 mg, and topiramate 200 mg would be the three best pharmacologic treatments based upon both weight gain effect and success rate.