Introduction <p>Contemporary trials of medications to treat hereditary angioedema (HAE) attacks define efficacy endpoints using Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) scales; these differ from the visual analog scale (VAS) and treatment effect questionnaire (TEQ) used in legacy recombinant human C1 esterase inhibitor (rhC1-INH) studies. This post hoc analysis aimed to evaluate pooled rhC1-INH trial data, mapped to contemporary HAE clinical trial endpoints and designs.</p> Methods <p>Pooling data from three rhC1-INH trials for acute HAE attacks (NCT00225147, NCT01188564, NCT00262301), this analysis applied results from a bookmarking study to convert TEQ and VAS measurements to PGI-S and PGI-C scales. Kaplan–Meier estimates were calculated for time to complete resolution (TTCR; defined as “none” on PGI-S) and time to onset of symptom relief (TOSR; defined as “a little better” on PGI-C at ≥ 2 consecutive time points within 12 h). Log-rank tests were used to determine differences between treatment groups.</p> Results <p>Across trials, 48 and 60 patients received rhC1-INH 50 U/kg and placebo, respectively. The most common attack locations were peripheral (47.9% and 41.7%, respectively) and abdominal (35.4% and 35.0%, respectively). Baseline attack severity was either severe or very severe in all patients. Median [95% confidence interval (CI)] TOSR was 0.75 h (0.55–1.50) with rhC1-INH and 8.00 h (3.00–8.05) with placebo (<i>P</i> &lt; 0.001). Median (95% CI) TTCR was 4.50 h (3.55–5.50) with rhC1-INH and 24.00 h (16.00– &gt; 24.00) with placebo (<i>P</i> &lt; 0.001).</p> Conclusion <p>This post hoc analysis confirmed that rhC1-INH, compared with placebo, is associated with significantly shorter TOSR and TTCR of HAE attacks.</p> Clinical Trial Registration <p>ClinicalTrials.gov: NCT00225147, NCT01188564, NCT00262301.</p>