Background: Tranexamic acid (TA) can prevent melanocyte activation by various stimuli. Combining TA with either hydroquinone 4% or Q-switched Nd:YAG laser may be associated with greater improvement of melasma. Objectives:We aimed to evaluate the efficacy and safety of oral TA alone and combined with either topical hydroquinone 4% or low-fluence 1064 nm Q-switched Nd:YAG laser in treatment of mixed melasma.Patients & Methods: Patients were randomly divided into three groups of 20 patients each. Group A were treated with oral TA 250 mg twice daily for three months; group B were treated with TA similarly combined with topical hydroquinone 4% cream; group C were treated with TA combined with two sessions of 1064 nm low-fluence Qswitched ND:YAG laser (850-1200 mJ/cm 2 , 4-5 Hz,spot size 4 mm) spaced 4 weeks apart. Patients were followed monthly for 9 months.Results: After cessation of therapy, the mean mMASI score was lowest in group B (2.34 ± 2.37) followed by groups A (6.38 ± 4.04) and C (7.24 ± 4.95).Mean percentage of mMASI score improvement was 35.91 ± 24.13, 77.47 ± 19.07, and 24.94 ± 27.79 in groups A, B, and C (p < 0.001). There was a significant reduction of telangiectasia in the three groups. Reported side effects were itching & irritation, post-inflammatory hyperpigmentation, and gastritis. Conclusion:Oral TA is a tolerable effective treatment modality for melasma.Combining hydroquinone 4% with oral TA is associated with a relatively earlier and better cosmetic outcome.