Objective To investigate the effects of dexmedetomidine combined with fentanyl on myocardial injury and renal function after heart valve replacement.Methods From January 2017 to December 2020, 86 patients with heart valve replacement under CPB in our hospital were selected as the research subjects. By random number table method, they were divided into experimental group and control group, with 43 patients in each group. Fentanyl was used for anesthesia induction and maintenance in both groups. The observation group was given dexmedetomidine 0.4 μg/(kg·h) by intravenous pump 10 min before anesthesia induction until the end of operation. Peripheral venous blood samples were collected from patients in the two groups to detect and compare levels of MAP, SpO₂, HR, CK-MB, Cystatin C (CysC), and BUN before treatment (T₀), during surgery (T₁), and 24 h after surgery (T₂). Visual analogue pain scale (VAS) was used to evaluate the pain degree in two groups at different time points. The incidence of adverse reactions within 14 days after operation was compared.Results The scores of MAP, SpO₂, HR, and VAS at different time points were different (P < 0.05). Among them, the scores of map, SpO₂, HR, and VAS were different at different time points (P < 0.05); there were differences in MAP, SpO₂, HR, and VAS scores between the two groups (P < 0.05); there were differences in the trend of MAP, SpO₂, HR, and VAS scores between the two groups with time (P < 0.05); Comparison of CK-MB, CysC and BUN levels between the two groups at different time points: there were differences in CK-MB, CysC, and BUN at different time points (P < 0.05); there was no difference in CK-MB, CysC, and BUN between the two groups (P > 0.05); there was significant difference in the change trend of CK-MB, CysC, and BUN with time between the two groups (P < 0.05). There was significant difference in the total incidence of respiratory depression, severe pain, and adverse reactions between the two groups (P < 0.05), which was lower in the observation group than in the control group. There was no significant difference in the incidence of nausea, vomiting, and hypotension between the two groups (P > 0.05).Conclusion Dexmedetomidine combined with fentanyl has a significant analgesic effect on heart valve replacement, with a low incidence of adverse reactions and no additional burden on hemodynamics, cardiac and renal functions, which is worthy of clinical promotion.