Background Current studies report mixed results in health status and health behaviors after a diagnosis of cancer. The aim of our study is to investigate potential differences in lifestyle factors among cancer survivors and cancer-free individuals in a prospective cohort study conducted in the United States. Methods Using data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial, 10,133 cancer survivors were identified and compared to 81,992 participants without cancer to evaluate differences in body mass index (BMI), smoking, NSAID use, and physical activity. Results Cancer survivors, compared to the cancer-free, were significantly less likely to engage in physical activity (odds ratio (OR) = 0.82, 95% CI = 0.77-0.88). Compared to those who were obese at baseline, cancer survivors were more likely to be at normal BMI at follow-up compared to the cancer-free (OR = 1.90, 95% CI = 1.42-2.54). Cancer survivors were less likely to report regular aspirin use as compared to the cancer-free population (OR = 0.86, 95 % CI = 0.82-0.92). Of the current smokers, cancer survivors were more likely to be former smokers at follow-up compared to the cancer-free (OR = 1.50, 95% CI = 1.30-1.74). Conclusion Upon stratification by baseline health markers, cancer survivors practice healthier lifestyle habits such as smoking cessation and maintenance of a healthy weight. However, cancer survivors are less likely to be physically active as compared to cancer-free individuals, regardless of baseline practices. Implications for cancer survivors For cancer survivors who reported poor health status and behaviors at baseline, a cancer diagnosis may encourage the practice of healthier lifestyle behaviors.