This research reports for the first time conductive anodic filament reliability of copper plated-through-vias with spacing of 75 – 200 µm in thin glass fiber reinforced organic packaging substrates with advanced epoxy-based and cyclo-olefin polymer resin systems. Reliability studies were conducted in halogenated and halogen-free substrates with improved test structure designs including different conductor spacing and geometry. Accelerated test condition (temperature, humidity and DC bias voltage) was used to investigate the effect of conductor spacing and substrate material influence on insulation reliability behavior. Characterization studies included gravimetric measurement of moisture sorption, extractable ion content analysis, electrical resistance measurement, impedance spectroscopy measurement, optical microscopy and scanning electron microscopy analysis and elemental characterization using energy dispersive x-ray spectroscopy. The accelerated test results and characterization studies indicated a strong dependence of insulation failures on substrate material system, conductor spacing and geometry. This study presents advancements in the understanding of failure processes and chemical nature of failures in fine-pitch copper plated-through-vias in newly developed organic substrates and demonstrates potential methods to mitigate failures for high density organic packages.