A meta-analysis compared emotional distress and psychological well-being across renal replacement therapies (RRTs) and examined whether differences could be explained by: (1) treatment modalities, (2) case mix, or (3) methodologic rigor. Standard meta-analytic procedures were used to evaluate published comparative studies. Successful renal transplantation was associated with: (1) lower distress (effect size, d = -0.43 SD) and greater well-being (d = 0. 62 SD) than in-center hemodialysis (CHD) and (2) lower distress (d = -0.29 SD) and greater well-being (d = 0.53 SD) than continuous ambulatory peritoneal dialysis (CAPD). CAPD was characterized by greater well-being (d = 0.18 SD) than CHD and CHD was associated with greater distress (d = 0.16 SD) than home hemodialysis. Although methodologic rigor and case-mix differences did not correlate with the magnitude of psychosocial differences across RRTs, 10 of the 12 comparisons (83%) were threatened by publication bias (ie, that nonsignificant comparisons may have been underrepresented in the published literature). Thus, although significant quality-of-life differences were evident across treatment groups, the types of patients representative of the various RRTs also differed significantly in terms of case-mix variables relevant to psychosocial well-being and emotional distress. Published findings indicating differential quality of life across RRTs may thus be attributable to: (1) valid differences in effective renal replacement, reduced medical complications, and lifestyles afforded by these treatment modalities; (2) case-mix differences in the patient samples selected to represent them in research comparisons; or (3) both of these alternative explanations.