Background and Aim <p>Majority trials evaluating fluid resuscitation in acute pancreatitis (AP) are small and contradictory. Fragility score is the minimum number of participants in a randomized controlled trial (RCT) whose outcome would have to change from non-event to event to overturn the results. We planned to evaluate the fragility of RCTs evaluating fluid resuscitation in AP.</p> Methods <p>After a systematic review of literature (CRD420261321080), fragility index (FI), reverse fragility index (RFI), and fragility quotient (FQ) were calculated. The results were labeled as fragile if FI ≤ 3, RFI ≤ 5, or FQ ≤ 0.10. Further sub-group comparisons of fragility scores were conducted as a secondary outcome.</p> Results <p>Among these 13 included studies, 26 primary or key secondary outcomes were evaluated. The mean FI was 2.83 (2.08) among the studies with significant results. The mean RFI was 5.35 (2.59) among the studies with non-significant results. The median FQ was 0.023 (interquartile range 0.02 to 0.078). The FI was ≤ 3 for 9 (75%) outcomes with significant results. The RFI was ≤ 5 for 8 (57.1%) with non-significant results, 23 (88.5%) of the outcomes were fragile as defined by FQ ≤ 0.10, and 25 (96.2%) of the results were fragile by any definition. The mean FI 3 (2) was lower as compared to mean RFI 5.35 (2.59), <i>p</i> = 0.01.</p> Conclusion <p>Majority of the studies evaluating fluid resuscitation in AP are fragile. Larger sample size or alternate designs should be considered in future trials evaluating fluid resuscitation.</p>