(Headache 2009;49:555-562) (1) To assess outcome at discharge for a consecutive series of admissions to a comprehensive, multidisciplinary inpatient headache unit; (2) To identify outcome predictors. An evidence-based assessment (2004) concluded that many refractory headache patients appear to benefit from inpatient treatment, underscoring the need for more research, including outcome predictors. The authors completed a retrospective chart review of 283 consecutive admissions over 6 months. The inpatient program (mean length of stay = 13.0 days) included intravenous and oral medication protocols, drug withdrawal when indicated, cognitive-behavior therapy, and other services when needed, including anesthesiological intervention. Patient-reported pain levels and consensus of medical staff determined outcome status. The 267 completers (94%) included 212 women and 55 men (mean age = 40.3 years, range = 13-74) from 43 states and Canada. The modal diagnosis was intractable, chronic daily headache (85%), predominantly migraine. Most (59%) had medication overuse headache (MOH), involving opioids (48%), triptans (16%), or butalbital-containing analgesics (10%). Psychiatric diagnoses included stress-related headache (82%), mood disorders (70%), anxiety disorders (49%), and personality disorders (PD, 26%). More patients with a PD (62%) had opioid-related MOH than those with no PD (38%), P < .005. Of the completers, 78% had moderate to significant pain reduction, with comparable improvement in mood, function, and behavior. Clinical factors predicting moderate-significant headache improvement were limited to MOH (84% vs 69%, P < .007) and presence of a PD (68% vs 81%, P < .03). Most patients (78%) improved following aggressive, comprehensive inpatient treatment. Maintenance of improvement is likely to depend on multiple post-discharge factors, including continuity of care, compliance, and home or work environment.