This study examined nicotine replacement effects and pre-quit smoking characteristics with respect to post-cessation weight gain in a primarily Mexican-American sample of Hispanic smokers. Hispanic smokers (108) were randomly assigned to receive either nicotine transdermal patch or placebo patch for 10 weeks, during which time smoking status and weight change were measured. The overall weight gain experienced by the successful quitters was greater than that experienced by non-quitters. Differences between quitters and non-quitters were significant for both females (2.0 vs. 0.86 kg; p < 0.05) and for males (2.3 vs. 1.2 kg; p < 0.05) at 6 weeks post-randomization. At the end of the 10-week treatment, only the females showed a significant difference in weight gain between the quitters and non-quitters (2.8 vs. 1.1; p < 0.01). Results of the random effects regression models for quitters indicated that the active group gained weight at a significantly lower rate than the placebo group (p = 0.047) for females, but not for males (p = 0.87). Years of smoking (p = 0.001) but not baseline cigarettes (p = 0.13) were significant predictors of weight for females, but not for males (p = 0.24 and 0.72, respectively). The use of nicotine patch treatment for smoking cessation effectively attenuated weight gain for successful female quitters compared with placebo-treated quitters. Identification of pre-quit smoking characteristics may prove useful in predicting who is most likely to gain weight when quitting smoking.