BACKGROUND: White spot lesions (WSLs) are one of the common problems which occur on enamel surface around bonded brackets following orthodontic treatment. AIM:Evaluate the effect of Er,Cr:YSGG (λ = 2780 nm) laser and 45S5 bioactive glass (BAG) paste either alone or in combination on re-mineralization of enamel white spot lesions.MATERIAL AND METHODS: 50 enamel samples with induced WSLs. There are 5 groups (n=10). Group 1, control; Group 2, 45S5 BAG paste treatment only; Group 3, Er,Cr:YSGG laser irradiated (0.5 W, 20 Hz, 10 s) alone, Group 4, 45S5 BAG paste treatment applied before irradiation with same laser parameters in group 3 and Group 5, 45S5 BAG paste treatment applied after laser irradiation. Enamel surface was assessed morphologically by stereomicroscope and Mineral content analysis by Energy Dispersive X-ray Analysis (EDXA). The results were statistically analyzed. RESULTS:EDXA revealed the highest Ca, Ca/P ratio and least C mass % in group 4. The highest P mass% in group 5. Stereomicroscopic results of outer enamel surface revealed that WSLs were reduced in group 2 while disappeared in group 3, 4 & 5. Group 4 showed more translucent enamel surfaces, whereas group 5 showed homogenous radio-opaque enamel surface. Stereomicroscopic results of enamel subsurface revealed the least M.B dye penetration depth in group 3 followed by 5, 4, 3, 2 and 1 respectively. CONCLUSIONS: 45S5 BAG paste treatment before Er,Cr:YSGG laser showed the best remineralized enamel surface with complete absence of WSLs.