BACKGROUND: Capillary blood testing has potential to improve accessibility and adherence for routine tests. Due to historical challenges with sample volume and quality, capillary blood is rarely used for diagnostic testing. These studies provide objective evidence that miniaturized assays and novel capillary collection technologies can enable equivalent results for important panels. METHODS: The studies evaluated equivalence of capillary blood testing using miniaturized assays and novel collection methods. We verified the performance of 20 miniaturized assays vs their unmodified versions. We then evaluated specimen equivalence across 39 analytes by comparing samples collected with novel capillary technologies vs samples collected with conventional technologies. For 38 analytes, specimen equivalence was evaluated vs conventional venous samples, and vs conventional capillary samples for 2 analytes with biological gradients (glucose and total CO2). RESULTS: Equivalence of miniaturized assays and novel capillary methods to conventional testing was demonstrated across all analytes. Method comparison of all 20 miniaturized assays highly correlated (Pearson r >
0.95) to unmodified versions of each test. Capillary blood collected with the novel collection procedure produced results equivalent to conventional methods, with 37 analytes performing equivalently to venous serum, glucose to both venous and conventional capillary serum, and total CO2 to conventional capillary serum. CONCLUSIONS: Capillary blood can be utilized for routine bloodwork. Issues with sample volume can be overcome by miniaturizing assays without compromising performance. Issues with sample quality can be overcome by novel capillary collection technologies, which additionally enable non-phlebotomist sample collection in a broad scope of healthcare settings.