To quantify and compare the course of health-related quality of life of immigrant native Italian-speaking and German-speaking patients before and after an interdisciplinary pain programme. Prospective cohort study with 1-12 month follow-up. Fibromyalgia, generalized widespread pain, and chronic non-specific back pain patients (Italian-speaking n = 96, German-speaking n = 199). Score changes measured with the Short Form 36 (SF-36) were compared with multivariate analysis using standardized mean differences (SMD), adjusted for sex, education and the baseline score. At baseline, health of the Italian-speaking patients was worse than for the German-speaking patients. Adjusted SMDs showed significantly better improvements in the German group compared with the Italian group: SF-36 Physical functioning SMD = 0.54 (at discharge) and 0.49 (at 12 months), General health SMD = 0.71 and 0.44, Vitality SMD = 0.43 and 0.48 in one sample. In the other sample, the corresponding SMDs were 0.06 (discharge), 0.50 (3 months) and 0.47 (6 months) for Bodily pain. State of health was better and health improvements were greater in German-speaking patients compared with Italian-speaking patients. Patients with a migration background may have special needs in therapeutic management, and addressing these might enhance the positive outcome in the short- and mid-term.