Girls and women are more frequently affected by headache than boys and men. The influence of gender on the effectiveness of headache therapies has so far been hardly investigated. We examined gender differences in the outpatient multimodal Dresden Child and Adolescent Headache Program DreKiP. We treated 140 patients with primary headache in a15-hour structured group program. At baseline (T0) and six (T1) and twelve months (T2) after the end of the program, data on headache-related limitation of daily activities (PedMIDAS) as well as headache frequency, intensity, and pain-related disability (P-PDI) were collected. Retrospectively, these data were analyzed separately for girls and boys. For 91patients (9-19years, median = 15; 71.4 % female) data were available for at least two measurement time points. Girls showed significantly higher headache frequency than boys at all time points (median headache days/last three months at T0: ♀43, ♂20; T1: ♀32, ♂12; T2: ♀28, ♂9) as well as numerically higher headache-related limitation of daily life. There were significant effects over time with a decrease in headache frequency (F(2.88) = 5.862; p = 0.004) and improvement in daily functioning (F(2.92) = 5.340; p = 0.006). There was no gender-specific treatment response. The DreKiP therapy shows effects in girls and boys with primary headache. Higher headache frequencies and everyday life restrictions in girls may have hormonal but also psychosocial causes and should be addressed in educational measures.