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 Q-switched 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.