Although gender differences in pain and analgesia are well known, it still remains unclear whether men and women vary in response to multimodal pain treatment. This study was conducted to investigate whether men and women exhibited different outcomes after an intensive multimodal pain treatment program. The daily outpatient program consisted of individual treatment as well as group therapy, with a total amount of therapy of 117.5h per patient. Overall, 496 patients (254 women) completed the multimodal program. Pretreatment parameters for pain, disability due to pain, pain duration, and pain chronicity stage, as well as age or psychiatric comorbidities, did not differ between genders. The average pain, measured with a Numeric Rating Scale, decreased after treatment of -1.54 (±1.96) with a large effect size (ES) of .911 for the total sample. However, there were considerable differences in the benefit for women (-1.83±2.12; ES 1.045) compared with men (-1.23±1.74; ES .758). Consistently, women (ES .694) improved more in pain-related disabilities in daily life than men (ES .436). These distinctions are not due to differences in pain duration, received medication, psychiatric comorbidities, pain chronicity stage, or application for a disability pension. Therefore, gender differences not only refer to chronic pain prevalence, pain perception, or experimental pain measurement, but also seem to have a clinically relevant impact on the response to pain therapy.