The objective was to use accumulated evidence to explore the association between processed meat intake and risk of colorectal cancer (CRC) and to investigate the reliability of associations by evaluating patterns of risk by study population characteristics and research quality parameters. We included 29 observational prospective cohort studies with relative risk estimates and 95% confidence intervals for CRC according to various levels of processed meat consumption. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I) tool. Data sources were PubMed and Embase up to January 2017. The summary relative risks for high versus low processed meat consumption and risk of CRC, colon, and rectal cancer were 1.13 (95% CI: 1.01, 1.26), 1.19 (95% CI: 1.09, 1.31), and 1.21 (95% CI: 0.98, 1.49), respectively. Similar estimates were observed for the dose-response analyses. Heterogeneity across studies was detected in most analytical models. The overall judgment showed that two out of 29 studies had a moderate risk of bias, 25 had a serious risk of bias, and 2 had a critical risk of bias. The bias domains most often rated critical were bias due to risk of confounding, bias due to missing data, and selective outcome reporting bias. Although this meta-analysis indicates a modest association between processed meat intake and an increased risk of CRC, our assessment of internal validity warrants a cautious interpretation of these results, as most of the included studies were judged to have serious or critical risks of bias.