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Background: The efficacy of panitumumab supplementation for colorectal cancer remains controversial. We conduct a systematic review and meta-analysis to explore the influence of panitumumab supplementation on treatment efficacy of colorectal cancer. Methods: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of panitumumab supplementation for colorectal cancer. This meta-analysis is performed using the random-effect model. Results: Five RCTs are included in the meta-analysis. Overall, compared with control group for colorectal cancer, panitumumab supplementation is associated with the increase in objective response for wild-type (WT) KRAS (RR = 1.70; 95% CI = 1.07–2.69; P = .03), but has no remarkable influence on objective response for mutant KRAS (RR = 0.92; 95% CI = 0.79–1.08; P = .32), objective response (RR = 1.35; 95% CI = 1.00–1.83; P = 0.05), progressive disease for WT KRAS (RR = 0.94; 95% CI = 0.85–1.02; P = .15), mortality (RR = 0.86; 95% CI = 0.69–1.08; P = .20), or mortality for WT KRAS (RR = 0.94; 95% CI = 0.84–1.05; P = .28). In addition, grade 3 and 4 adverse events are found to be higher in panitumumab group than those in control group (RR = 1.17; 95% CI = 1.08–1.27; P = .0001; Fig. 8). Conclusions: Panitumumab supplementation can provide some improvement in objective response for colorectal cancer patients with WT KRAS, but results in the increase in grade 3 and 4 adverse events.