OBJECTIVE Exercise may be associated with increased health-related quality of life (QoL) in patients with cancer, but it is not prescribed as standard care during or after cancer treatment. We systematically reviewed the methodological quality of, and summarised the evidence from, randomised controlled trials (RCTs). A meta-analysis was performed to examine the effectiveness of exercise in improving the QoL in patients with cancer, during and after medical treatment. METHODS RCTs that met the PICO (Patient Intervention Control Outcome) format were included in this study. 16 RCTs were identified through a search of Embase, Medline (OvidSP) and the Cochrane Library. These trials were reviewed for substantive results and the methodological quality was assessed using the Delphi criteria list. RESULTS Exercise interventions differed widely in content, frequency, duration and intensity. Based on the meta-analysis, exercise improved QoL significantly in patients with cancer as compared to usual care (mean difference 5.55, 95% CI (3.19 to 7.90), p<0.001). Other outcomes closely related to QoL, such as fatigue and physical functioning, also improved. CONCLUSIONS Exercise has a direct positive impact on QoL in patients with cancer, during and following medical intervention. Exercise is a clinically relevant treatment and should be an adjunct to disease therapy in oncology.