Bispectral Index Scale (BIS)-guided closed-loop delivery of anesthetics has been extensively studied. We performed a meta-analysis of all the randomized clinical trials comparing efficacy and performance between BIS-guided closed-loop delivery and manually controlled administration of total IV anesthesia. Scopus, PubMed, EMBASE, and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and closed-loop delivery systems versus manually controlled administration of total IV anesthesia in any surgical setting. Exclusion criteria were duplicate publications and nonadult studies. Twelve studies were included, randomly allocating 1284 patients. Use of closed-loop anesthetic delivery systems was associated with a significant reduction in the dose of propofol administered for induction of anesthesia (mean difference [MD] = 0.37 [0.17–0.57], P for effect <0.00001, P for heterogeneity = 0.001, I2 = 74%) and a significant reduction in recovery time (MD = 1.62 [0.60–2.64], P for effect <0.0001, P for heterogeneity = 0.06, I2 = 47%). The target depth of anesthesia was preserved more frequently with closed-loop anesthetic delivery than with manual control (MD = −15.17 [−23.11 to −7.24], P for effect <0.00001, P for heterogeneity <0.00001, I2 = 83%). There were no differences in the time required to induce anesthesia and the total propofol dose. Closed-loop anesthetic delivery performed better than manual-control delivery. Both median absolute performance error and wobble index were significantly lower in closed-loop anesthetic delivery systems group (MD = 5.82 [3.17–8.46], P for effect <0.00001, P for heterogeneity <0.00001, I2 = 90% and MD = 0.92 [0.13–1.72], P for effect = 0.003, P for heterogeneity = 0.07, I2 = 45%). When compared with manual control, BIS-guided anesthetic delivery of total IV anesthesia reduces propofol requirements during induction, better maintains a target depth of anesthesia, and reduces recovery time.