A simple, precise, and cost-effective reverse phase ion pair chromatographic (RP-IP-HPLC) method was developed and validated for the determination of Ephedrine Hydrochloride in a nasal ointment. A simple and fast extraction protocol was developed for the effective recovery of the analyte, and for this purpose, Bromhexine Hydrochloride was used as the internal standard. The mobile phase consisted of MeOH, Sodium Lauryl Sulfate (SLS) 49.8 mM, triethylamine (ET3N) in the ratio of 65:34.6:0.4%, respectively, with pH = 2.20. The detection of the compounds was carried out at 206 nm, and we used a PDA detector. A short run time was achieved with retention times of 6.3 min and 9.8 min for ephedrine hydrochloride and the internal standard, respectively. The proposed method was validated according to ICH guidelines. Linearity was confirmed in the range of 50–150 μg/mL. Recoveries results were within the range of 98–102% and precision < 2% for the analyte in spiked blank matrix. Robustness testing was conducted via a fractional factorial experimental design. The method was found to fulfill the required specifications for specificity and stability for both standard solutions and samples, as well and applied to the determination of ephedrine hydrochloride in nasal ointments produced by the Greek Military Pharmaceutical Laboratories.