The Missoula-Vitas Quality-of-Life Index (MVQOLI) is a unique tool specifically designed to measure quality of life (QOL) in advanced illness in a palliative care setting. The aim of this study was to explore its cross-cultural validity. We used a culturally adapted version in a local language, Luganda, and tested the MVQOLI-M in 200 patients with advanced AIDS in urban Kampala, Uganda. Content validity was assessed using the content validity ratio approach. Reliability was assessed using Cronbach's alpha (alpha), and test-retest reliability was evaluated using the intraclass correlation coefficient. All items and domains were rated content valid and there was good construct validity. The instrument demonstrated good internal consistency (alpha=0.83). The transcendence domain was the best predictor of overall QOL. The MVQOLI-M is an acceptable, valid, and reliable measure of QOL for people with advanced AIDS and findings demonstrate the importance of measuring the transcendence domain in QOL in advanced illness.