Creatine (CRE) and caffeine (CAF) have been used as ergogenic aids to improve exercise performance. The present study reviewed the current evidence supporting the additional use of CAF intake during or after the CRE loading on exercise performance. The search was carried out in eight databases, with the methodological quality of the studies assessed via the QualSyst tool. From ten studies that met the criteria for inclusion, six had strong, three moderate, and one weak methodological quality. CAF was ingested ∼1 h before the performance trial (5-7 mg.kg-1) after a CRE loading period (5-6 days with 0.3 g.kg-1.d-1) in five studies, with the combination CAF + CRE providing additional ergogenic effect compared to CRE alone in three of these studies. Furthermore, CAF was ingested daily during the CRE loading protocol in five studies, with CAF showing additive benefits compared to CRE alone only in one study (3 g.d-1 of CRE during 3 days + 6 mg.kg-1 of CAF for 3 days). The combination CAF + CRE seems to provide additional benefits to exercise performance when CAF is acutely ingested after a CRE loading. There is, however, no apparent benefit in ingesting CAF during a CRE loading period.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.2007470.