Objectives To evaluate the effect of urinary trypsin inhibitor (UTI) or Ulinastatin on postoperative course and clinical outcomes in patients with cardiopulmonary bypass. Methods We searched PubMed, Embase, Web of Science, and Cochrane Library for the keywords UTI and Cardiopulmonary bypass (CPB). The primary outcome measure was the intensive care unit length of stay (ICU LOS), and results were stratified for relevant subgroups (dosage of UTI). The effects of UTI on mechanical ventilation duration (MVD), hospital LOS, renal failure incidence (RFI), and all-cause mortality were studied as secondary outcomes. Results Twelve randomized controlled trials (enrolling 1620 patients) were evaluated. Eleven studies pooled for subgroup analysis showed that using UTI persistently or with a considerable amount would lead to a shorter ICU LOS (95% CI, − 0.69 to − 0.06; P = 0.0001). Ten studies showed that UTI could shorten MVD in patients (95% CI, − 1.505 to − 0.473; P < 0.0001). RFI generally showed a more favourable outcome with UTI treatment (95%CI, 0.18–1.17; P = 0.10). And the current evidence was insufficient to prove that UTI could reduce the hospital LOS (95% CI, − 0.22 to 0.16; P = 0.75) and the all-cause mortality rate (95% CI, 0.24–2.30; P = 0.60). Conclusions Various subsets of UTI treatment suggested that UTI could shorten ICU LOS, and it is associated with the dosage of UTI. Considering the substantial heterogeneity and lack of criteria for UTI dosage, more evidence is needed to establish a standard dosing guideline.