Observational studies demonstrate an association between physical activity and improved outcomes in breast and colon cancer survivors. To test these observations with a large, randomized clinical trial, an intervention that significantly impacts physical activity in these patients is needed. The Active After Cancer Trial (AACT) was a multicenter pilot study evaluating the feasibility of a telephone-based exercise intervention in a cooperative group setting. Sedentary (engaging in <60 min of recreational activity/week) breast and colorectal cancer survivors were randomized to a telephone-based exercise intervention or usual care control group. The intervention was delivered through the University of California at San Diego; participants received ten phone calls over the course of the 16-week intervention. All participants underwent assessment of physical activity, fitness, physical functioning, fatigue and exercise self-efficacy at baseline and after the 16-week intervention. One hundred and twenty-one patients were enrolled through ten Cancer and Leukemia Group B (CALGB) institutions; 100 patients had breast cancer and 21 had colorectal cancer. Participants randomized to the exercise group increased physical activity by more than 100 versus 22% in controls (54.5 vs. 14.6 min, P = 0.13), and experienced significant increases in fitness (increased 6-min walk test distance by 186.9 vs. 81.9 feet, P = 0.006) and physical functioning (7.1 vs. 2.6, P = 0.04) as compared to the control group. Breast and colorectal cancer survivors enrolled in a multicenter, telephone-based physical activity intervention increased physical activity and experienced significant improvements in fitness and physical functioning. Lifestyle intervention research is feasible in a cooperative group setting.