Abstract Objectives A P -value <0.05 is one metric used to evaluate the results of a randomized controlled trial (RCT). We wondered how often statistically significant results in RCTs may be lost with small changes in the numbers of outcomes. Study Design and Setting A review of RCTs in high-impact medical journals that reported a statistically significant result for at least one dichotomous or time-to-event outcome in the abstract. In the group with the smallest number of events, we changed the status of patients without an event to an event until the P -value exceeded 0.05. We labeled this number the Fragility Index; smaller numbers indicated a more fragile result. Results The 399 eligible trials had a median sample size of 682 patients (range: 15–112,604) and a median of 112 events (range: 8–5,142); 53% reported a P -value <0.01. The median Fragility Index was 8 (range: 0–109); 25% had a Fragility Index of 3 or less. In 53% of trials, the Fragility Index was less than the number of patients lost to follow-up. Conclusion The statistically significant results of many RCTs hinge on small numbers of events. The Fragility Index complements the P -value and helps identify less robust results.