Objective: To evaluate the therapeutic effects of intravenous infusion using intravenous indwelling needles (IIN) versus peripherally inserted central catheters (PICC) in patients with acute leukemia during maintenance treatment. Methods: Eighty-six patients with acute leukemia admitted to the First Affiliated Hospital of Baotou Medical College from July 2022 to March 2023 were randomly divided into the IIN group and the PICC group, with 43 patients in each group. Results: Significant differences were observed between the two groups in terms of the number of punctures and puncture time (P<0.05). Although the intubation cost was lower in the IIN group than in the PICC group, the maintenance treatment duration was shorter in the IIN group (P<0.05). There were no significant differences between the two groups in terms of disease symptoms, treatment-related toxicity, and side effects (P>0.05). However, anxiety, treatment compliance, and patient satisfaction were significantly lower in IIN group compared to the PICC group (P<0.05). Additionally, the incidence of vein-related complications in the IIN group was higher than in the PICC group (P<0.05). Conclusion: Compared with intravenous indwelling needles, PICCs demonstrate superior application outcomes. Although the cost of PICC placement is relatively high, its ability to prolong maintenance treatment, alleviate patient anxiety, reduce vein-related complications, and improve treatment compliance makes it a valuable method worth promoting.