This study examines the effects of telephone and mail interview methods on the measurement of health-related quality of life. One thousand six hundred ninety individuals aged 25–66 were interviewed randomly either by telephone or by mail. Health-related quality of life was assessed with the German SF-8. Although respondents in the telephone survey were more willing to participate (77.4% vs. 47.5%) the difference in the accessibility of publicly available address and telephone records meant that overall more people were interviewed by mail than by telephone (53.2% vs. 46.8%). No differences occurred in terms of the sociodemographic makeup. Telephone respondents gave a more positive account of the mental dimension of their health-related quality of life; whereas mail interviews led to a better rating of the respondents' physical well-being. Gender-specific analyses indicate a slight discrepancy in the influence of the method of interviewing on men and women. Further differences were identified concerning the variance in the existence of ceiling and floor effects and the correlation between items. Found differences are small but at least to be valued as relevant in certain settings. Therefore, we approve the use and development of factors of amendment.