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BACKGROUND: As a part of continuous quality initiatives, while moving from triple bags to quadruple bags, we undertook a study to compare platelet-rich plasma (PRP) and buffy-coat (BC) methods with respect to all blood components (red blood cells [RBCs], random donor platelet concentrate [RDPC], and fresh frozen plasma [FFP]) prepared by PRP and BC methods. MATERIALS AND METHODS: It was a prospective analysis of different physical and quality parameters of RDPC, RBC, and FFP prepared out of 100 whole blood (WB) donations. Of these, 50 WB units were processed by PRP method using Triple bags and 50 WB units by BC method, using quadruple (top and bottom) bags, with an attached integral filter. RESULTS: RBC prepared by BC method had higher hematocrit (61.3 ± 1.91% vs. 56.03 ± 3.37%; P < 0.05) and lower white blood cell (WBC) contamination (6.3 × 10 4 ± 6.1 vs. 5.41 × 10 5 ± 2.5; P < 0.05) in comparison to prepared by PRP method. Higher PLT yield (7.67 × 10 10 ± 1.8 vs. 6.47 × 10 10 ± 1.5; P < 0.05) and lower WBC count (8.24 × 10 3 ± 1.1 vs. 1.5 × 10 4 ± 2.1; P < 0.05) was observed in RDPC prepared by BC method than PRP derived. CD62P expression was lower in RDPC prepared by BC method (31.46 ± 9.7%; P < 0.05) as compared to PRP method (43.35 ± 12.5%; P < 0.05). The BC method also resulted in increased plasma yield (210.56 ± 18.54 ml vs. 187.92 ± 12.93 ml; P < 0.05) in FFP in comparison to PRP method. CONCLUSION: The blood components produced from WB by the BC method have laboratory variables suggestive of superior quality than those produced by the PRP method.