A simple, rapid, precise and accurate reverse-phase HPLC method was developed and validated for the simultaneous determination of emtricitabine, tenofovir and efavirenz in commercial tablets. The method has shown adequate separation for emtricitabine, tenofovir and efavirenz. Separation was achieved on Inertsil C18 (250 mm × 4.6mm; 5 μm) column using isocratic method with 0.1%OPA: Methanol (55:45) system at room temperature and the detection was carried out at 260 nm using photodiode array (PDA) detector. The linearity of the proposed method was investigated in the range of 20-60μg/ml (r2=0.9999), 30-90μg/ml (r2=0.9999), 60-180μg/ml (r2=0.9988) for emtricitabine, tenofovir and efavirenz respectively. The limit of detection (LOD) was 0.066, 0.1540 and 0.353 for emtricitabine, tenofovir and efavirenz respectively. The limit of quantification (LOQ) was 0.290, 0.0773 and 1.176 for emtricitabine, tenofovir and efavirenz respectively. The relative standard deviation (RSD) of six replicates is less than 2%. This HPLC method is applied successfully to the simultaneous quantitative analysis of emtricitabine, tenofovir and efavirenz in commercial tablets.