Physical activity can confer many benefits on cancer survivors, including relief of persistent symptoms related to cancer treatment. To evaluate the effect of a motivational interviewing (MI) intervention on increasing physical activity (Community Healthy Activities Model Program for Seniors questionnaire) and improving aerobic fitness (6-minute walk), health (Medical Outcomes Study Short-Form 36), and fatigue (Schwartz Cancer Fatigue Scale) in cancer survivors. A secondary purpose was to evaluate whether the effect of MI on physical activities depended on self-efficacy. Fifty-six physically inactive adult cancer survivors (mean=42 months since completion of treatment) were assigned randomly to intervention and control groups. The MI intervention consisted of one in-person counseling session followed by two MI telephone calls over 6 months. Control group participants received two telephone calls without MI content. Outcomes were measured at baseline, 3 months, and 6 months, and were analyzed using multilevel modeling. The results of the MI intervention explained significant group differences in regular physical activities (measured in caloric expenditure per week), controlling for time since completion of cancer treatment (p<.05). Aerobic fitness, physical and mental health, and fatigue were not different between groups. In the intervention group, individuals with high self-efficacy for exercise at baseline increased their physical activity more than those with low self-efficacy (p<.05). In the control group, increases in physical activity did not depend on self-efficacy. Use of MI may increase physical activity in long-term cancer survivors, especially in persons with high self-efficacy for exercise. Multilevel modeling analysis revealed individual changes that would not have been shown by analysis of group means. Future studies with larger samples or more intense MI interventions may show changes in aerobic fitness, physical and mental health, and fatigue.