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Smoking has been suggested to increase the rate of perioperative complications including soft-tissue complications, to decrease the rate of fracture union, and to prolong healing time. The purpose of our study was to systematically evaluate and analyze the literature regarding the relationship between smoking and healing following operative treatment of long-bone fractures.We searched the MEDLINE, Embase, and Cochrane databases by pairing the search terms “smoking,” “tobacco,” and “nicotine” with the terms “fracture,” “nonunion,” delayed union,” and “healing.” Articles and citations were evaluated for relevance. Inclusion and exclusion criteria were established to maintain data quality for analysis. Relevant information was independently extracted and compared to ensure agreement. The methodological quality of the studies was determined. A random-effects model was used. The adjusted odds ratios (ORs) and frequency-weighted means for the primary and secondary outcome measures were calculated.Our initial search identified 7110 articles. Of the 237 articles that underwent further evaluation of the abstract, nineteen (seven prospective and twelve retrospective cohort studies) were included. The adjusted OR of nonunion in the smoking group compared with the nonsmoking group was 2.32 (95% confidence interval [CI], 1.76 to 3.06; p < 0.001). An increased nonunion rate was observed in smokers with a tibial fracture (OR, 2.16; 95% CI, 1.55 to 3.01; p < 0.001) and those with an open fracture (OR, 1.95; 95% CI, 1.3 to 2.9; p < 0.001). For all fractures, the mean healing time was longer for smokers (30.2 weeks; 95% CI, 22.7 to 37.7 weeks) than for nonsmokers (24.1 weeks; 95% CI, 17.3 to 30.9 weeks) (p = 0.18). Trends toward more superficial and deep infections of postoperative or traumatic wounds in smokers were noted; however, the differences in superficial and deep infection rates were not significant (p = 0.13 and p = 0.33, respectively).Smoking significantly increased the risk of nonunion of fractures overall, tibial fractures, and open fractures. Nonsignificant trends toward increased time to union in all fractures and toward increased postoperative rates of superficial and deep infections were noted in smokers compared with nonsmokers.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.