OBJECTIVE: Several studies explored the effects of caffeine on isometric handgrip strength, but their findings varied. Therefore, the aim of this review was to perform a meta-analysis of studies exploring the effects of caffeine on isometric handgrip strength. METHODS: Search for studies was performed through five databases (Academic Search Elite, Cochrane Library, PubMed/MEDLINE, SPORTDiscus, and Scopus) with additional secondary searches. RoB 2 scale was used to evaluate the risk of bias of the included studies. The effects of caffeine vs. placebo were analyzed in a random-effects meta-analysis. RESULTS: Sixteen studies were included (n = 353; n = 34 females). The studies were classified as having "some concerns" (possible bias from the randomization process and in the measurement of the outcome) on the RoB 2 scale. In the main meta-analysis, caffeine ingestion enhanced isometric handgrip strength (d: 0.17; 95% confidence interval [CI]: 0.10, 0.23; p < 0.001). In subgroup analyses, an ergogenic effect of caffeine on isometric handgrip strength was found when consumed in small doses (1-3 mg/kg; d: 0.20; 95% CI: 0.10, 0.30; p < 0.001), moderate-to-high doses (5-7 mg/kg; d: 0.15; 95% CI: 0.07, 0.23; p < 0.001), liquid form (d: 0.19; 95% CI: 0.09, 0.30; p < 0.001), and capsule form (d: 0.15; 95% CI: 0.06, 0.23; p < 0.001). CONCLUSIONS: Overall, individuals interested in the acute enhancement of isometric handgrip strength may consider caffeine supplementation in small or moderate-to-high doses. However, these ergogenic effects were very small and were observed mostly among male participants.