<i>Background:</i> To analyze the therapeutic results of recombinant interleukin-2 (rIL-2) left in the cysts after transvaginal ultrasound (US)-guided drainage of endometriomas as an alternative to surgery. <i>Methods:</i> Prospective and randomized clinical trial. A total of 25 consecutive patients were included. Two transvaginal US-guided punctures were performed, and 3 million IU of rIL-2 were left in the aspirated cysts once (group I) or both (group II) times according to randomization. <i>Main Outcome Measures:</i> Clinical results, prevented surgeries, and recurrences. <i>Results:</i> Results were moderate or good in only 16% of subjects at 3 months and in 33% of subjects at 6 months after treatment in group I; these numbers were 66 and 33%, respectively, in group II. Differences were not statistically significant. However, the evolution of symptoms, endometriomas, and CA-125 revealed the low efficacy of rIL-2 left intracyst as well as a poor control of the clinical manifestations. After 1 year, 20% (group I) and 73% (group II) of patients had to be operated; after 2 years, these numbers were 55 and 82%, respectively. <i>Conclusions:</i> Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts, without using endometrial suppressive therapy with GnRH analogues as done in previous studies, has low efficacy. Recurrences are even more frequent after the use of two rIL-2 doses.