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Background and Aim. RNA extraction is a commonly used technique in molecular biology. In recent years, commercially available RNA extraction kits have largely replaced conventional approaches. However, these commercial kits are expensive and are not readily available in many resource-constrained institutions and laboratories. This study therefore compared the performance of the conventional acid guanidinium thiocyanate-phenol-chloroform (AGPC) extraction method to QIAamp® Viral RNA Mini Kit (QIAGEN, Cat. No. 52906) and OxGEn RNA Kit (OxGEn Molecular Solutions, GE-009) to build an in-house RNA extraction technique from blood and oral swab samples. Method. In a comparative experimental cross-sectional study, RNA was extracted from oral swabs and blood samples from 25 healthy individuals at the Department of Molecular Medicine, KNUST. RNA was extracted by the manual AGPC extraction method and commercial RNA extraction kits. The quantity (ng/μl) and purities (260/280 nm) of the extracted RNA were measured spectrophotometrically using the IMPLEN NanoPhotometer® N60. The presence of RNA in the extracts was confirmed using 2% agarose gel electrophoresis. Statistical analyses were conducted using R language. Results. The yield of RNA extracted from blood and oral swab samples using modified AGPC was significantly higher compared to the commercial methods (p