Purpose: A systematic review and meta-analysis of studies that specifically compared immediate to conventional loading of single implant crowns was conducted and the overall treatment effect was estimated. Materials and Methods: MEDLINE, the Cochrane Controlled Trials Register, and bibliographies of relevant primary and review articles were searched. Randomized and nonrandomized controlled studies that compared immediate with conventional loading of single implant crowns were selected according to strict criteria. From the 105 articles screened, five studies with 248 implants were analyzed. The meta-analysis was prepared in accordance with the Quality of Reporting of Meta-analyses (QUOROM) statement. Descriptive and outcome data were extracted using specially designed data extraction forms. The data were entered into MIX software for meta-analysis using a fixed effects model, relative risk, and 95% confidence interval (CI). Results: Immediate loading of single implant crowns was associated with a significantly higher risk of implant failure (relative risk: 5.07, 95% CI: 2.00 to 12.84, P .001). Pooling of randomized controlled trials showed similar results, although the difference was not statistically significant. Immediate nonocclusal loading was also associated with worse outcomes when compared to conventional loading (relative risk: 4.76, 95% CI: 1.74 to 13.02, P = .002). Conclusions: This systematic review and meta-analysis shows that better outcomes are currently achieved using conventional loading of single implants with crowns, as opposed to immediately loaded ones, which are at a higher risk of failure. Further adequately powered clinical trials are needed. Caution with immediate loading of implants with crowns as a standard of care for single tooth replacement is recommended.