The green analysis has acquired increased importance in different fields including pharmaceutical analysis. However, the majority of chromatographic methods still use large volumes of toxic and non- degradable organic solvents. This study displays a green HPLC assay method for simultaneous estimation of two moxifloxacin combinations: moxifloxacin/dexamethasone and moxifloxacin/prednisolone. Simultaneous separation of each of moxifloxacin binary mixtures was achieved on a reversed phase Thermo scientific MOS-1 Hypersil C8 column (250 mm × 4.6 mm i.d., 5-μm particle size) using an eco-friendly isocratic eluent; ethanol: water containing 0.05% triethanolamine (90:10, v/v, pH 4.5). The assay was completed for each combination within <6 min applying a flow rate of 1.0 mL/min. UV-detector was adjusted at 240 nm for the first 4.0 min and later at 280 nm using time programming technique. The suggested method allowed the simultaneous analysis of each of moxifloxacin combinations in their laboratory prepared binary mixtures in different pharmaceutical ratios. Eye drops containing either moxifloxacin/dexamethasone or moxifloxacin/prednisolone were successfully analyzed by the described procedure. Assessment of method greenness has been carried out using three different tools. The method is considered an eco-friendly alternative of conventionally developed HPLC methods regarding usage of safe solvents and chemicals, production of minimal waste amount and short time of analysis. The suggested method could also be helpful in the routine quality control analysis of the investigated binary mixtures with least harmful effect on the environment or human being.