Abstract Objectives We aimed to identify potential laboratory causes of suboptimal liver biopsy quality and sought to implement corresponding measures to improve biopsy adequacy. Methods We prospectively measured the number and size of tissue fragments and the amount of portal tracts in 200 consecutive pediatric medical liver biopsies before and after quality improvement processes were initiated. Results We identified laboratory-related tissue fragmentation as a significant cause of low biopsy adequacy. The principal approaches to reduce fragmentation included establishment of multistep monitoring of tissue integrity, adjustment of specimen-processing conditions, and laboratory staff education and awareness. These adjustments collectively led to lower overall tissue fragmentation (decreasing from 59% to 24%, P < .01) and higher biopsy adequacy rates (increasing from 32% to 56%, P < .01). The number of evaluable portal tracts increased from 4.4 to 5.7 portal tracts per centimeter of core biopsy tissue (P < .01). Conclusions We demonstrated a sustainable improvement in the overall quality of pediatric needle core liver biopsies by reducing tissue fragmentation. Effective laboratory adjustments included monitoring of tissue integrity, modifications of processing conditions, and laboratory staff education.