Objective To compare and analyze the efficacy and safety of different methods for injecting polidocanol in the treatment of venous malformations. Methods The medical records of patients with venous malformations in our hospital from April 2021 to April 2023 were analyzed retrospectively, and they were divided into control group ( n = 38) and observation group ( n = 20) according to different treatment methods. Control group was injected with polidocanol under ultrasound guidance, while observation group was injected with polidocanol under digital subtraction angiography (DSA) monitoring. Therapeutic effects of observation group and control group after 3-6 months of treatment were compared and analyzed, and complications that can be used to reflect the safety of treatment in two groups were collected and recorded. Results After treatment, the total effective rates of observation group and control group were 97.37% (37/38) and 75.00% (15/20) respectively, with significant differences (both p < .05). After 3-6 months of treatment, 13 complications occurred in observation group, while 16 occurred in control group. The number of complications in observation group was 6, with an incidence rate of 15.78%; while that in control group was 9, with an incidence rate of 45.00%, with a significant difference ( p < .05). There were no significant differences among other baseline data, age and complications between two groups (all p > .05). Conclusion Injection of polidocanol in patients with venous malformations under DSA monitoring was more effective and safer.