Introduction Acute adverse drug reactions (ADRs) in day-care chemotherapy are not uncommon and are easily manageable on most occasions. However, sometimes they may lead to untoward events. It is paramount to document and analyze such events in contemporary medical oncology practice for the best utilization and planning of available personnel and resources. Objective Our objective was to analyze the acute ADRs occurring in day-care cancer chemotherapy settings. Materials and Methods ADRs reported in a day-care cancer chemotherapy setting, during the administration of chemotherapy, were prospectively observed and analyzed from 01 June 2020 to 31 December 2020. ADRs were classified into anaphylactic, allergic, and gastrointestinal (GI) (nausea/vomiting/heart burns/chest tightness). All ADRs were graded according to the Common Terminology Criteria for Adverse Events Version 5.0. Suspected drugs, time to reaction, and corrective measures were analyzed. Results During the study period, a total of 10,120 sessions of day-care chemotherapy were administered. ADRs were noticed in 118 cases (1.18%). Among the reported ADRs, the mean and median age of the patients in this study was 52 years (21–88). Women outnumbered men (n = 81, 68.64% vs n = 37, 31.36%). Anaphylactic reactions (50.92%) were the most common followed by allergic (25.15%) and GI reactions (23.93%). No grade IV reaction was observed. Oxaliplatin-induced allergic reactions (n = 28, 23.73%) were noted most frequently. In majority of sessions (n = 93, 78.81%), the same chemotherapy regimen was readministered and completed uneventfully after the administration of antihypersensitivity medications. Conclusion Serious ADRs are rare in current day-care chemotherapy administration. Most acute ADRs were of mild grade and successfully managed with antihypersensitivity medication.