The study evaluated leukocyte esterase (LE) and nitrite reagent pad usefulness in canine urine using multiple time endpoints and decision thresholds. Whole and sedimented urine samples from 116 client-owned dogs were analyzed with reagent strips from four manufacturers. Results for LE and nitrite were recorded every 30 s up to 150 s using “trace” and “+” positive thresholds and compared to microscopic urine sediment analysis and culture results. Sedimented urine assessed at 150 s with a “trace” positive threshold for LE had significantly or trending higher sensitivity (brand dependent) for pyuria detection compared with manufacturer recommendations. Using these parameters, LE sensitivity and negative likelihood ratio were 66.67–89.47%, and 0.13–0.37, respectively. Following manufacturer recommendations, LE specificity and positive likelihood ratio were 96.91–100% and 17.02–30.63, respectively. Nitrite performance for pyuria and bacteriuria detection was poor for all conditions. LE reagent pads are a useful screening test for pyuria detection using sedimented urine and a “trace” positive threshold at 150 s, whereas LE use with traditional manufacturer recommendations is a good confirmatory test for pyuria detection. Nitrite reagent pads are not useful for pyuria or bacteriuria detection.