Objective: To evaluate the safety of applying the “Wait-and-See” (W&S) strategy in rectal cancer patients with clinical complete response (cCR) after neoadjuvant chemoradiotherapy (NCRT). Methods: The clinical studies comparing using W&S strategy and radical surgery (RS) in rectal cancer patients with cCR after NCRT were collected by searching several foreign databases. After screening for inclusion, data extraction and quality assessment, Meta-analysis was performed on the variables that included local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), disease-free survival (DFS) and overall survival (OS) by using Stata/SE 12.0 software. Results: Eleven studies with moderate to high quality were included, involving 847 patients, with 378 cases in W&S group and 469 cases in RS group. The results of Meta-analysis showed that W&S group was superior to RS group in terms of LR (RR=6.20, 95% CI=2.68–14.30, P=0.000), 2-year OS (RR=1.05, 95% CI=1.01–1.10, P=0.029) and 3-year OS (RR=1.09, 95% CI=1.03–1.15, P=0.004), while no differences were noted with regard to DM, CRD, or 2-, 3- and 5-year DFS as well as 5-year OS between the two groups (all P>0.05). Conclusion: W&S strategy is safe and feasible for some patients who achieved cCR after NCRT, but this strategy requires rigorous screening criteria and standardized follow-up program. Meanwhile, large sample size and multicentric, prospective randomized controlled trials are urgently expected to verify this treatment approach.