BACKGROUND: Clonidine is still the most popular additive for caudal regional anesthesia. Aim of the present quantitative systematic review was to assess the efficacy and safety of the combined use of clonidine and local anesthetics in comparison with caudal local anesthetics alone. METHODS: The systematic search, data extraction, critical appraisal and pooled analysis were performed according to the PRISMA statement. The systematic search included the Central register of controlled trials of the Cochrane Library (to present), MEDLINE (1966 to present), EMBASE (1980 to present) and CINAHL (1981 to present). Relative risk (RR), mean difference (MD) and the corresponding 95% confidence intervals (CI) were calculated using the Revman((R)) statistical software for dichotomous and continuous outcomes. RESULTS: Twenty randomized controlled trials (published between 1994 and 2010) including 993 patients met the inclusion criteria. There was a longer duration of postoperative analgesia in children receiving clonidine in addition to local anesthetic (MD: 3.98 h; 95% CI: 2.84-5.13; P < 0.00001). Furthermore, there was a lower number of patients requiring rescue analgesics in the clonidine group (RR: 0.72; 95% CI: 0.57-0.90; P = 0.003). The incidence of complications (e.g., respiratory depression) remained very low and was not different to caudal local anesthetics alone. CONCLUSIONS: There is considerable evidence that caudally administered clonidine in addition to local anesthetics provides extended duration of analgesia with a decreased incidence for analgesic rescue requirement and little adverse effects compared to caudal local anesthetics alone.