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Background: Hereditary angioedema (HAE) is a rare, potentially fatal genetic disorder characterized by unpredictable attacks of bodily swelling that substantially impair patients' quality of life (QoL). Lanadelumab is approved for long-term prophylaxis (LTP) in patients with HAE; however, there are limited real-world data that compare lanadelumab with other treatments to guide patient care. Objective: The objective was to describe real-world QoL and related outcomes of patients with HAE who received lanadelumab versus other LTP. Methods: Data were drawn from a real-world, cross-sectional survey of physicians and their consulting patients with HAE in the United States from January 2023 to January 2024. Physician-reported attack and disease severity, pain, fatigue, QoL, and patient-reported outcomes were compared among patients receiving lanadelumab or other LTP. Results: Physicians reported data on 86 patients treated with lanadelumab and 84 treated with other LTP. A statistically significantly higher proportion of patients receiving lanadelumab had no chronic pain (58.1%) and no chronic fatigue (51.2%) at the time of the survey than those receiving other LTP (38.1% [p = 0.0023] and 34.9% [p = 0.0037], respectively). More patients receiving lanadelumab had "very good" physician-reported QoL and less patient-reported QoL impairment at the time of the survey compared with those receiving other LTP (p = 0.0102). A higher proportion of patients receiving lanadelumab compared with other LTP reported complete satisfaction overall with their treatment (30.2% versus 17.9%, respectively; p = 0.0144) and complete satisfaction with the efficacy of their treatment (44.2% versus 11.9%, respectively; p < 0.0001). Conclusion: In this real-world study, physicians reported a higher proportion of patients receiving lanadelumab had no chronic pain or fatigue compared with those receiving other LTP. Both physicians and patients reported higher QoL in those receiving lanadelumab. Continued real-world research in patients with HAE to further assess the effect of lanadelumab on QoL will help guide patient care.