Background: A parallel-group randomized controlled trial (RCT) was conducted to evaluate the effect of combining the interscalene brachial plexus block (IBPB) with Intravenous–inhalation combined anesthesia to isolated Intravenous–inhalation anesthesia in the upper extremity fractures surgery of elderly patients. Methods: One hundred elderly patients who underwent upper extremity surgery were randomly assigned to received isolated Intravenous–inhalation combined anesthesia (group CI, n = 50) and IBPB associated with Intravenous–inhalation combined anesthesia (group NB, n = 50). Associated side effects, recovery time after operation, as well as the dose of intraoperative vasoactive agents and auxiliary drugs were noted. Results: The two groups were not significantly different in gender (P = 0.539), ages (P = 0.683) and weight (P = 0.212). Five patients (10%) in the group NB and 17 patients (34%) in the group CI suffered from preoperative hypotension (P = 0.004). Besides, lower incidence of other adverse effects such as mental stress, incision pain and hypertension were also found in the group NB; however, the differences were not statistically significant (P > 0.05). The consumption of general anesthetics in the group NB was significantly less than that of the group CI (propofol, P = 0.004; lsoflurane, P < 0.001), and the recovery time of the group NB was significantly shorter than that of the group CI (P = 0.020). Conclusion: Combining IBPB with Intravenous–inhalation combined anesthesia in elderly patients hold a greater potential for upper extremity fractures surgery due to its improved clinical effectiveness and fewer side effects.