A simple reverse phase HPLC method was developed for the determination of the phenoxymethylpenicillin in pharmaceutical dosage. Efficient chromatographic separation was achieved on Lichrospher 100 RP-18e, 250 x 4.0mm 10μ column from waters-2998 isocratic ode, with simple mobile phase combination of phosphate buffer : methanol : water (8:42:50). Adjust pH of the mixture to 3.5 ± 0.05 with ortho phosphoric acid used. The flow rate was 1.2ml/ min and effluent was monitored at 254 nm. The retention time of phenoxymethyl penicillin was 16.529 minutes. The proposed method is simple, selective, reproducible, sensitive and accurate with good precision. Some of the methods were proved to be superior to most of the reported methods. All these proposed methods for estimation of selected drug phenoxymethylpenicillin was successfully applied in pharmaceutical formulations