BACKGROUND: Weight loss interventions have been successfully delivered via several modalities, but recent research has focused on more disseminable and sustainable means such as telephone- or Internet-based platforms. OBJECTIVE: The aim of this study was to compare an Internet-delivered weight loss intervention to a comparable telephone-delivered weight loss intervention. METHODS: This randomized pilot study examined the effects of 6-month telephone- and Internet-delivered social cognitive theory-based weight loss interventions among 37 cancer survivors. Measures of body composition, physical activity, diet, and physical performance were the outcomes of interest. RESULTS: Participants in the telephone intervention (n=13) showed greater decreases in waist circumference (-0.75 cm for telephone vs -0.09 cm for Internet, P=.03) than the Internet condition (n=24), and several other outcomes trended in the same direction. Measures of engagement (eg, number of telephone sessions completed and number of log-ins) suggest differences between groups which may account for the difference in outcomes. CONCLUSIONS: Cancer survivors in the telephone group evidenced better health outcomes than the Internet group. Group differences may be due to higher engagement in the telephone group. Incorporating a telephone-based component into existing weight loss programs for cancer survivors may help enhance the reach of the intervention while minimizing costs. More research is needed on how to combine Internet and telephone weight loss intervention components so as to maximize engagement and outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01311856; https://clinicaltrials.gov/ct2/show/NCT01311856 (Archived by WebCite at http://www.webcitation.org/6tKdklShY).