Background: Melasma is a common dermatosis in both men and women showing varying degrees of success with treatment. Relapse of pigmentation in melasma after treatment is a common problem in dark skin types that necessitates treatment with novel alternative modalities with better efficacy. Aim: To compare the effectiveness of intradermal platelet-rich plasma vs. 1064 nm Qs Nd-YAG in patients of melasma in a split face comparative study conducted in a Dermatology center over a period of 6 months. Methods: A comparative split face prospective study of 20 female patients of Fitzpatrick skin type IV-V with mixed resistant type of melasma and bilateral involvement of the face were enrolled for the study. Platelet-rich plasma (PRP) was injected intradermally at 2 weeks interval for seven sittings in one half of the face and Qs Nd-YAG was done every week for 12 weeks on the other half of the face. The results were assessed clinically by Hemi-modified MASI score at the end of every 2 weeks. Patients were counselled to continue strict sun protection measures. Patient satisfaction was noted at baseline, 4 weeks, 8 weeks, and 12 weeks. Patients were followed up for 3 months to see for any relapse of the pigmentation and the follow-up results were compared for both modalities of treatment. Results: Comparison of Hemi-mMASI score in both groups showed statistically significant improvement of pigmentation on completion (i.e., at the end of 12 weeks) and not in successive follow-up results every 2 weeks. The subjective assessment was made by PGAIS (Physician global aesthetic improvement scale). Patient satisfaction levels (assessed by SGAIS-Subject global aesthetic improvement scale) also showed significant improvement in successive weeks of treatment in both the groups. Few patients had mild redness and burning post procedure which resolved spontaneously after few hours. Patients were followed up for 3 months to see for reappearance of melasma. The split side treated with PRP showed less reappearance of pigmentation than the side treated with Qs Nd-YAG laser. Conclusion: From this study we concluded that PRP shows a significant improvement in pigmentation in mixed resistant melasma in 12 weeks of treatment with less chances of relapse after 3 months of treatment as compared with Qs Nd-YAG laser. PRP may be used as a first-line treatment in mixed, resistant melasma cases and also as an excellent maintenance therapy in these cases. Limitations: Desired sample size could not be achieved and a longer follow-up period of 6 months could not be materialized.