Many previous published methods for the quantitative determination of propranolol (PRN) in human plasma have poor recoveries and were not validated according to the FDA guideline. The aim of this study is to develop a simple HPLC method for detecting PRN in human plasma and to validate it so that it can be applied to a clinical study. Chromatographic separation was achieved using a mixture of a mobile phase consisting of 160 ml water, 180 ml methanol, 70 ml acetonitrile, 2.5 ml acetic acid, and 125 microl triethylamine (v/v). The pH of the whole mixture was adjusted to 3.4. A flow rate of 0.5 ml/min was employed throughout with a 15 microl injection volume. Detection was done using a UV detector at 291 nm. The validated method was linear for concentrations ranging from 15-180 ng/ ml with a good separation and specificity for both PRN and its internal standard, oxprenolol (OXP), with excellent recoveries, precision, and accuracies. The limit of detection (LOD) and limit of quantification (LOQ) were 1 and 10 ng/ml, respectively. The stability studies demonstrated that PRN is stable in the autosampler vials and also up to 3.5 months. To the authors' knowledge, the recovery, that ranged between 97.9-102.7%, is the highest among all previously reported methods that used HPLC with UV detection. The developed and validated method for PRN analysis is excellent and applicable to a clinical study.