The aim of this study was to investigate the variables affecting headache occurrence in patients with multiple sclerosis (MS). Seventy-two MS patients with comorbid headaches completed a 28-item questionnaire. This evaluation assessed each patient's demographics, headache description and modifying factors, social history, and impact on quality of life. Our patients reported a wide spectrum of headache presentations, characteristics, and resulting disability. We discuss the patterns in our data in the context of current hypotheses regarding headache and MS causality. In our patients, migraines with aura strongly correlated with MS exacerbations, suggesting that they might be useful as a marker for flare-up onset. Patients' pain descriptions varied based on their headache frequency, history, and relationship to MS progression. Due to the severity of headache in MS patients and resulting impact on their activities of daily living, a thorough analysis of headache presentation is warranted in such patients.