A new, simple, precise, accurate, stability-indicating, and rapid high-performance thin-layer chromatography (HPTLC) method was developed and validated for the determination of ondansetron hydrochloride in pure form and pharmaceutical formulations. The method used Merck HPTLC aluminum plates precoated with silica gel 60 F254 as the stationary phase. The mobile phase consisted of chloroform–methanol–ethyl acetate (7:2:1, v/v). This system was found to give a compact spot of ondansetron (RF value of 0.67 ± 0.011); ondansetron was subjected to acid and alkali hydrolysis, oxidation, and photodegradation. The wavelength of TLC scanner was set at 302 nm for both detection and quantitation. The calibration curves were linear over the range of 25–500 ng spot−1. The limit of detection was 4.9 ng spot−1, and the limit of quantitation was 14.7 ng spot−1. The proposed analytical method was validated according to the International Conference on Harmonization (ICH) guidelines, and the results were acceptable. The propo...