A growing global aging population is presenting more opportunities for health professionals to interact with other cultures. The specific aims of this study were to: (1) compare the quality of life of midlife men and women in Australian and Taiwan; and (2) to explore the impact of country of residence and gender on quality of life. A cross-sectional survey was conducted using census data and a probability proportional sampling (PPS) strategy on a general population of men and women aged 40-59 years-old who live permanently in Taiwan and Australia. The sample consisted of 278 Australians and 398 Taiwanese men and women. Analysis showed that country of residence does have an impact on quality of life with significant differences seen between midlife Australian and Taiwanese men and women (F 4, 666 = 59.31, p less than 0.001). The results suggest that midlife Australian men and women have a better quality of life than midlife Taiwanese men and women. The mean score for the four domains of quality of life by gender indicated that midlife women consider that they have a better quality of life than midlife men in both Australia and Taiwan. Midlife Australian men in this study reported they are more dissatisfied with their sleep and rest (x [squared] = 10.57, df = 4, p = 0.03) and more dissatisfied with their sexual activities (x [squared] = 9.42, df = 4, p = 0.05) in contrast to midlife Australian women. This study has addressed and contributed to the assessment of multi-cultural quality of life research and has important implications for both health providers and policy makers of both countries.