Background. Health-Related Quality of Life (HRQoL) studies are gaining importance. Yet there is a dearth of crossculturally validated generic HRQoL instruments for Indian adolescents. Two HRQoL instruments, namely World Health Organization Quality of Life-Brief (WHOQOL-BREF) and Pediatric Quality of Life inventoryTM 4.0 (PedsQL), are widely used internationally, with both measuring four domains (physical, psychological/emotional, social relations and environment/school) but each having different questions with 26 in the former and 23 in the latter. This study was done among adolescents in the city of Lucknow to evaluate the psychometric properties of PedsQL and compare its performance with previously validated and culturally revised WHOQOL-BREF. Methods. This cross-sectional study was conducted in February 2010 after institutional ethical approval. Data were collected by a self-administered, predesigned questionnaire in which items of PedsQL and revised WHOQOL-BREF were intermingled. Reliability, content and construct validity were evaluated for PedsQL. Convergent validity of PedsQL with revised WHOQOL-BREF was calculated for domains with similar questions. Results. Parents of 76.5% adolescents (385/503) provided consent. Mean age of adolescents was 13.6 years (1.6 SD and 44.7% were girls). PedsQL showed substantial reliability (Cronbach alpha=0.82, p<0.00001) but poor to fair validity as compared to revised WHOQOL-BREF. Conclusions. For Indian adolescents, PedsQL is a reliable and valid instrument. However, on comparison with revised WHOQOL-BREF, PedsQL has poor to fair validity. We conclude that revised WHOQOL-BREF is a better HRQoL instrument for Indian adolescents. {\textcopyright} The National Medical Journal of India 2012.