Objective: Limited evidence exists concerning whether combined pharmacotherapy is more effective than monotherapy for increased smoking abstinence and post-cessation weight gain prevention. This research investigated the effect of combined pharmacotherapy on smoking abstinence and post-cessation weight change. Methods: A meta-analytic review of Randomized Controlled Trials (RCTs) published between January 1990 and July 2016 was conducted across PubMed, International Pharmaceutical Abstracts, Web of Science, and Cochrane Library. Aggregate fixed effects were estimated for continuous abstinence and mean post-cessation weight change. Keyword search terms included: “smoking cessation,” “naltrexone”, “varenicline”, and “bupropion”. Results: Eight RCTs with 2,513 participants were included. Aggregate fixed effect estimates revealed an increase in continuous smoking abstinence (OR = 1.81, p < .001) and mean decrease in post-cessation weight change (-.15 kg, p = .001). Decreased weight change was observed at 6-8 weeks follow-up (-.14 kg, p = .02). Increased mean weight change was observed among varenicline plus nicotine patch abstainers (.21 kg, p = .01), whereas bupropion plus NRT pharmacotherapies showed decreased mean weight change (-.15 kg, p = .01). Conclusion: Combination pharmacotherapy generates increased smoking abstinence and small short-term post-cessation weight change among abstainers, particularly among bupropion plus NRT when compared against varenicline plus nicotine patch.