Copyright © 2016 International Anesthesia Research Society. BACKGROUND: Many studies have compared propofol-based anesthesia with inhalational anesthesia. Results from several studies have shown improved postoperative analgesia after propofol anesthesia, but other studies showed contradictory results. There are no large prospective studies that compare postoperative pain after propofol versus inhalational anesthesia. This meta-analysis was designed to focus on this question. METHODS: A systematic literature search for randomized controlled trials that compared propofol-based anesthesia with volatile agents-based anesthesia in adults undergoing surgery was conducted. Published data were pooled for the meta-analysis with Review Manager (ie, RevMan). The main outcomes included postoperative pain intensity, opioid consumption, need for rescue analgesics, and time to first analgesia. RESULTS: Thirty-nine clinical trials with a combined subject population of 4520 patients came within the purview of this meta-analysis. The investigated volatile agents included isoflurane, sevoflurane, and desflurane. Compared with inhalational anesthetics, the propofol use was associated with a reduced postoperative pain intensity at rest at 30 minutes, 1 hour, and 12 hours (mean difference in pain scores, 30 minutes, -0.48 [visual analog scale, 0-10]; 99% confidence interval [CI], -1.07 to 0.12, P = 0.04) and reduced morphine-equivalent consumption 0 to 24 hours postoperatively (mean difference in morphine-equivalent consumption, -2.68 mg; 99% CI, -6.17 to 0.82; P = 0.05). Fewer patients required postoperative rescue analgesics during 0 to 24 hours after surgery under propofol anesthesia (risk ratio, 0.87; 99% CI, 0.74-1.03; P = 0.04). In addition, patients anesthetized with propofol required administration of postoperative analgesia later than those anesthetized with volatiles (mean difference in time to first analgesic administration, 6.12 minutes; 99% CI, 0.02-12.21; P = 0.01). Considering that Z statistic in RevMan 5.3 does not perform optimally in highly heterogeneous samples among groups or many combinations of groups with small sample sizes, a P value of <.01 was considered statistically significant. On the basis of this threshold, none of the aforementioned results are statistically significant. CONCLUSIONS: The current results are affected by substantial heterogeneity, which makes it difficult to predict significant differences in postoperative pain control between propofol anesthesia and inhalational anesthesia. Further large, randomized controlled trials are needed to corroborate these results and to detect differences (if any) between propofol and inhalational anesthesia on postoperative pain.