Background. Current analytic methods applied to multidimensional health-related quality of life (HRQOL) data do not borrow strength across analyses and do not produce summary estimates of effect. Objectives. To compare a random effects modelling approach for the analysis of multidimensional HRQOL data to the following: (1) separate analyses for each dimension; (2) O'Brien's global test procedure; and (3) multivariate analysis of variance (MANOVA). Research Design. Randomized clinical trial comparing 3 treatments (Trimethoprim-Sulfamethoxazole [TS], Dapsone-Trimethoprim [DT], and Clindamycin-Primaquine [CP] for Pneumocystis carinii pneumonia [PCP]). Subjects. Patients with PCP enrolled in AIDS Clinical Trials Group Protocol 108. Measures. A 33-item battery assessing 7 dimensions of HRQOL: physical functioning, pain, energy, general health perceptions, disability, pulmonary symptoms, and constitutional symptoms. Results. Analyses focused on changes in score from baseline to Day 7 (n = 145). Separate analyses for each dimension suggested a trend favoring CP versus TS, but using a Bonferroni correction no differences were statistically significant. O'Brien's global procedure for a test of no-treatment effect versus superiority of one treatment yielded P = 0.07. MANOVA did not reveal significant differences among treatment groups. A random effects model using fixed treatment and dimension effects and separate random effects for each person showed a significant overall treatment effect (P = 0.02); changes in scores for CP averaged 10 points greater than for TS. Conclusions. Random-effects models provide a flexible class of models for analyzing multidimensional quality of life data and estimating treatment effects because they borrow strength across dimensions.