Clinically evident Anastomotic Leakage (AL) remains one of the most feared complications after colorectal resections with primary anastomosis. The primary aim of this systematic review and meta-analysis was to determine whether Prophylactic Drainage (PD) after colorectal anastomoses confers any advantage in the prevention and management of AL. Systematic literature search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases for randomized studies comparing clinical outcomes of patients with Drained (D) or Undrained (UD) colorectal anastomoses performed for any cause. Four randomized controlled trials comparing D and UD patients undergoing colorectal resections with primary anastomosis were included for quantitative synthesis. In total, 1120 patients were allocated to group D (n = 566) or group UD (n = 554). The clinical AL rate was 8.5% in the D group and 7.6% in the UD group, with no statistically significant difference (P = 0.57). Rates of radiological AL (D: 4.2% versus UD: 5.6%; P = 0.42), mortality (D: 3.6% versus UD: 4.4%; P = 0.63), overall morbidity (D: 16.6% versus UD: 18.6%, P = 0.38), wound infection (D: 5.4% versus UD: 5.3%, P = 0.95), pelvic sepsis (D: 9.7% versus UD: 10.5%, P = 0.75), postoperative bowel obstruction (D: 9.9% versus UD: 6.9%, P = 0.07), and reintervention for abdominal complication (D: 9.1% versus UD: 7.9%, P = 0.48) were equivalent between the two groups. The present meta-analysis of randomized controlled trials investigating the value of PD following colorectal anastomoses does not support the routine use of prophylactic drains. Copyright © 2019 Elsevier Inc. All rights reserved.