Objective - To test the hypothesis that feline calcium oxalate uroliths are intrinsically more resistant to comminution via shock wave lithotripsy (SWL) than canine calcium oxalate uroliths through comparison of the fragility of canine and feline uroliths in a quantitative in vitro test system. Sample population - Calcium oxalate uroliths (previously obtained from dogs and cats) were matched by size and mineral composition to create 7 pairs of uroliths (1 canine and 1 feline urolith/pair). Procedure - Uroliths were treated in vitro with 100 shock waves (20 kV; 1 Hz) by use of an electrohydraulic lithotripter. Urolith fragmentation was quantitatively assessed via determination of the percentage increase in projected area (calculated from the digital image area of each urolith before and after SWL). Results - After SWL, canine uroliths (n = 7) fragmented to produce a mean ± SD increase in imagearea of 238 ± 104%, whereas feline uroliths (7) underwent significantly less fragmentation (mean image area increase of 78 ± 97%). The post-SWL increase in fragment image area in 4 of 7 feline uroliths was < 50%, whereas it was > 150% in 6 of 7 canine uroliths. Conclusions and clinical relevance - Results indicate that feline calcium oxalate uroliths are less susceptible to fragmentation via SWL than canine calcium oxalate uroliths. In some cats, SWL may not be efficacious for fragmentation of calcium oxalate nephroliths or ureteroliths because the high numbers of shock waves required to adequately fragment the uroliths may cause renal injury.