Results from cohort studies of adult weight gain and risk of colorectal cancer are inconsistent. We conducted a systematic review and meta-analysis of prospective studies assessing the association of change in weight/body mass index with colorectal cancer risk. We searched Scopus and Web of Science up to June 2014 and supplemented the search with manual searches of the reference lists of the identified articles. Thirteen studies published between 1997 and 2014 were pooled by using a random-effects model, and potential heterogeneity was explored by fitting meta-regression models. The highest weight gain category, measured by weight/body mass index, compared with a reference category, was associated with increased risk of colorectal cancer (hazard ratio (HR) = 1.16, 95% confidence interval (CI): 1.08, 1.24), whereas no association was found for weight loss (HR = 0.96, 95% CI: 0.89, 1.05). There was no suggestion of heterogeneity across studies. For dose response, a 5-kg weight gain was associated with a slightly increased risk of colorectal cancer (HR = 1.03, 95% CI: 1.02, 1.05), with some heterogeneity observed (I(2) = 42%; P = 0.02), which was partially explained by sex (ratio of HRs = 1.03, 95% CI: 1.00, 1.07). In this meta-analysis, gain in weight/body mass index was positively associated with colorectal cancer risk.