<h3>Objective:</h3> To assess the impact of spontaneous intracranial hypotension (SIH) on quality-of-life (QoL). <h3>Background:</h3> SIH is a debilitating condition that typically produces orthostatic headache and limits upright time. It is often difficult to detect, diagnose, and treat, profoundly affecting patients’ QoL. <h3>Design/Methods:</h3> We conducted a cross-sectional survey of patients with confirmed (n=59) and clinically suspected (n=36) SIH evaluated from 2016 to 2022. Participants completed the following validated measurements online (REDCap V 11.2.2): SF-36 (general well-being), PHQ-9 (depression), GAD-7 (anxiety), FACIT-Sp-12 (spiritual well-being), and HIT-6 (headache impact). Subsequently, willing participants were interviewed to administer the Columbia-Suicide Severity Rating Scale (C-SSRS) assessing suicidal behavior and ideation. <h3>Results:</h3> 95 of 234 patients (41%) meeting inclusion criteria completed the questionnaires. The average age was 51.1 years (SD: 15.5), predominantly female (69.5%), Caucasian (91.6%), and married (69.5%). 74.5% scored within the most severe headache category on the HIT-6. SF-36 scores were significantly worse (p < 0.0001) compared to the general population. 49.1% scored in the moderate or worse depression range (>10) and 25.4% scored for moderate or worse anxiety (>10). FACIT scores strongly correlated (p<0.001) with HIT-6 (−.54), SF-36 Mental Component (r=.66), PHQ-9 (r=−.65) and GAD-7 (r=−.65). 67 respondents completed the C-SSRS of whom 64.2% had endorsed a wish to be dead, and 22.4% had demonstrated suicidal behavior. Symptom-free SIH patients (n = 22) scored significantly better than symptomatic patients and similar to the general population. <h3>Conclusions:</h3> SIH is associated with severe headache pain and high rates of depression, anxiety, and disability, affecting basic activities of daily living. Individuals with confirmed and suspected SIH had similar levels of head pain, depression, anxiety and suicidality in our cohort. Symptom-free individuals following successful treatment or spontaneous remission showed improved outcomes comparable to the general population. Improved identification and treatment of SIH are imperative to improving patients’ QoL. <b>Disclosure:</b> Mr. Liaw has nothing to disclose. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan/Abbvie. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven Pharmaceuticals. Dr. Friedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Friedman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Impel. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Friedman has received personal compensation in the range of $0-$499 for serving as a Consultant for Teva. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zosano. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium Pharmaceuticals. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Impel. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Reviews. Dr. Friedman has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink Neurology . The institution of Dr. Friedman has received research support from Zosano. The institution of Dr. Friedman has received research support from Allergan. The institution of Dr. Friedman has received research support from Spinal CSF Leak Foundation. Dr. Friedman has a non-compensated relationship as a Program Co-Chair, Scottsdale Headache Symposium with American Headache Society that is relevant to AAN interests or activities. Dr. Friedman has a non-compensated relationship as a Medical Advisor with Spinal CSF Leak Foundation that is relevant to AAN interests or activities. Mr. McCreary has nothing to disclose.