Ullas BatraIt is well known that patients with cancer are at an increased risk of severe COVID-19. There are no reports that depict the differences in outcomes in cancer patients between the two waves of the pandemic. This is a real-world experience aimed at characterizing the differences in demographics, clinical features, treatment details, and outcomes in COVID-19-positive cancer patients between the two pandemic waves. This was a prospective study of all COVID-19-positive cancer patients attending our specialty out-patient department at Rajiv Gandhi Cancer Institute and Research Centre between March 2020 and November 2020 (1st wave) and April 2021 and June 2021 (second wave). All patients diagnosed to have COVID-19 by real-time polymerase chain reaction (RT-PCR) with a biopsy-proven solid organ malignancy attending the medical oncology out-patient department were included during both the waves. A total of 300 patients with proven SARS-CoV-2 infection by either RT-PCR or cartridge based nucleic acid amplification test were encountered, of which 123 were encountered during the first wave of the pandemic and 177 during the second wave. The case fatality rate of the first wave was 9.8%, with a 15-day case fatality rate of 5.6%, whereas for the second wave, it was 13% and 7.2%, respectively. Twelve patients succumbed to COVID-19 disease in the first wave and 23 succumbed in the second. There were no statistically significant correlations; however, the death in the second wave tended to occur more in younger male patients, with comorbidities and history of smoking. There was no relation with ongoing cancer-directed treatment or chemotherapy. Our study is unique in comparing characteristics of the two most important COVID-19 waves and treatment patterns in cancer patients from a single center. The second wave showed a higher CFR, hospital admission rate, and higher frequency of respiratory complications; however, there was no relation to cancer-directed therapy and COVID-19, thus reiterating the fact that cancer treatment should not be halted in the event of a COVID-19 infection.