The aim of the study was to provide an overview of the effect of exercise interventions on subjective quality of life (QoL) across adult clinical populations and well people, and to systematically investigate the impact of the exercise setting, intensity and type on these outcomes. From a systematic search of six electronic databases, 56 original studies were extracted, reporting on 7937 sick and well people. A meta-analysis was conducted on change in QoL from pre- to post-intervention compared with outcomes from a no-exercise control group, using weighted (by the study’s sample size) pooled mean effect sizes and a fixed-effects model. Significant differences in outcome were found when treatment purpose was compared; prevention/promotion (well populations), rehabilitation, or disease management. Three to six months post-baseline, a moderate positive effect of exercise interventions was found for overall QoL in rehabilitation patients (effect size [ES] = 0.55), but no significant effect for well or disease management groups (ES = 0.11 and ES = -0.00 respectively). However, physical and psychological QoL domains improved significantly relative to controls in well participants (ES = 0.22 and ES = 0.21 respectively). Psychological QoL was significantly poorer relative to controls in the disease management group (ES = -0.26). This pattern of results persisted over one year. With some exceptions, better overall QoL was reported for light intensity exercise undertaken in group settings, with greater improvement in physical QoL following moderate intensity exercise. The implications for future practice and research are discussed.