Background: Rapid drug desensitization (RDD) is a procedure that provides temporary tolerance to chemotherapeutics for appropriate patients who experience hypersensitivity reactions (HSR), which allow them to continue their treatments. Due to the labor-intensive and time-consuming nature of the commonly used multiple-bag RDD procedure, there is a need to develop an alternative protocol. We aimed to share our experiences with single-bag RDD in patients experiencing HSRs with chemotherapeutics. Methods: The study was conducted by retrospectively reviewing the files of patients who experienced immediate-type HSRs to chemotherapeutics and underwent single-bag RDD. The severity of HSRs was classified according to the Brown grading system. Prick and/or intradermal skin tests were performed with the relevant agents. The protocols were applied as a single-bag, 12-step process. Results: The study comprised 46 patients (women/men, 35/11; mean ± standard deviation age, 55.9 ± 11.9 years; 27 HSRs to platinums; 16 HSRs to taxanes; and 3 HSRs to biologic agents). Nine patients (19.6%) had an initial HSR of grade 1, 26 patients (56.5%) had an initial HSR of grade 2, and 11 patients (23.9%) had an initial HSR of grade 3. The skin testing result with the responsible drug was positive in 15 of 42 (35.7%), and the rate of positive responses in patients with grade 1, 2, and 3 initial HSRs was 37.5%, 33.3%, and 40%, respectively. A total of 163 single-bag RDDs procedures were performed, and 17 breakthrough reactions (BTR) occurred during the procedure (five of these reactions [29.5%] were grade 1; nine [53.9%] were grade 2; three [17.6%] were grade 3). Of these BTRs, 16 occurred with platinums and one with rituximab; no BTRs were observed with taxanes. In conclusion, 99.3% of the total 163 single-bag RDD procedures were successfully completed. Conclusion: Our experience indicates that single-bag RDD can be a safe and effective alternative that saves time and labor in appropriate patients.