Computed tomography (CT) is the most commonly used radiological response evaluation method in contemporary oncology. However, it may not be optimally suitable for assessment of oncolytic virus treatments because of paradoxical inflammatory tumor swellings, which result from virus treatments, particularly when viruses are armed with immunostimulatory molecules. Here we investigated the prognostic utility of CT and [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oncolytic virus treatments. We also investigated possible appearance of false-positive FDG signals in FDG-PET imaging of humans and hamsters treated with oncolytic adenoviruses. First, immunocompetent Syrian hamsters were treated with intratumoral adenovirus injections, tumor growth was followed up, and [(18)F]-FDG-uptake was quantitated with small animal PET/CT. Second, we describe a retrospective patient series, essentially 17 individual case reports, of advanced cancer patients treated with oncolytic adenoviruses in the context of an Advanced Therapy Access Program (ATAP) who underwent radiological response evaluation with both contrast-enhanced CT and FDG-PET. Third, we collected a retrospective case series of radiological response and survival data of 182 patients treated with oncolytic adenoviruses in ATAP to evaluate the prognostic reliability of CT and FDG-PET. Overall, responses in CT and FDG-PET correlated well with each other and were equally reliable as prognostic markers for long survival after oncolytic adenovirus treatment. Interestingly, we observed that new FDG-avid lymph nodes appearing in FDG-PET after virus treatments may represent inflammatory responses and therefore should not be interpreted as treatment failure in the absence of other signs or verification of disease progression. We also observed indications that FDG-PET might be more sensitive in detection of responses than tumor size.