<p>The past decades have witnessed a growing interest in patient-centric sampling, including dried capillary blood microsampling. Despite its advancements, a key issue lies in interpreting dried capillary blood results against existing plasma-based reference ranges. To address this challenge, various methodologies to convert dried capillary blood concentrations to plasma equivalents have been proposed. This study systematically evaluates and compares different methodologies for converting dried capillary blood results to venous plasma results using clinical pharmacokinetic (PK) data of paracetamol and metabolites as a case study. Paired capillary volumetric absorptive microsampling (cVAMS) and venous plasma samples were collected from 55 patients. For each analyte, cVAMS results were converted using multiple approaches, including conversion based on the median (time-dependent) capillary-to-plasma ratio, Passing-Bablok regression analysis, linear mixed-effects modeling and the hematocrit (Hct). Performance was assessed by comparing the agreement between converted cVAMS concentrations and actual plasma results to pre-defined analytical and clinical acceptance criteria. All approaches, except Hct-based conversion, yielded acceptable results for all analytes, with minor variations in analytical performance. Estimated C_max and AUC_6h values (and corresponding 90% confidence intervals) calculated based on the converted cVAMS results were within bio-equivalence criteria for all conversion approaches, except Hct-based conversion for one analyte. Both from analytical and clinical perspectives, this study demonstrated the reliability of different approaches to convert capillary blood microsampling-based to plasma-based results. The framework utilized in this study may guide future microsampling (PK) studies aiming at switching from collecting samples from the reference matrix to an alternative capillary blood matrix.</p> Graphical Abstract <p></p>