•A novel ejector-expansion refrigeration cycle is proposed, analyzed and optimized.•The system performance is assessed and compared for six refrigerants.•The proposed system yields its best performance with R1234ze refrigerant.•Proposed system performs 5.5–11% better than the standard ejector-expansion system.•Exergy efficiency of proposed system is 12.5–27.5% higher than the vapor compression system. A novel ejector-expansion refrigeration cycle (EERC) is proposed, analyzed and optimized in this paper. Assuming a constant-pressure mixing model for ejector simulation, a detailed and comprehensive thermodynamic analysis, based on the first and second laws, is conducted and the system performance is investigated for six proper refrigerants. The proposed system is then optimized considering the exergy efficiency as the objective function and a comparison is made with the standard EERC and conventional vapor compression refrigeration system at the optimized conditions. The results indicated that, among the six investigated refrigerants, R1234ze is the best one for which the proposed system has 5.7% and 15.5% higher exergy efficiency values than the standard EERC and conventional vapor compression refrigeration cycle, respectively, at condensing temperature of 40 ∘C and evaporation temperature of 5 ∘C. Also, it is concluded that for higher condensing and lower evaporating temperatures the value of performance improvement is higher.