PURPOSE: We aimed to conduct a systematic review and meta-analysis comparing the outcomes of subdermal implants and levonorgestrel intrauterine system (LNG-IUS) in reproductive-aged women. METHODS: In April 2024, we searched Pubmed, Embase and Cochrane trials using the search terms: "etonogestrel", "levonorgestrel" and "randomized controlled trials". We identified 2862 results comparing the LNG-IUS to subdermal implants. Randomized controlled trials (RCTs) were selected with no restrictions on language or year of publication. RESULTS: We include six RCTs comprising 1503 patients. R Studio was used for statistical analysis. Subdermal implants were associated with a higher risk of dissatisfaction (OR 2.42
95% CI 1.47-3.98), acne (OR 2.21
95% CI 1.21-4.04), weight gain (OR 4.63
95% CI 1.96-10.63), and device removal due to side effects (OR 2.02
95% CI 1.20-3.41) compared to the LNG-IUS group. Subgroup analysis indicated that irregular bleeding may be influenced by gynecological conditions, and the risk of new ovarian cyst detection was lower in healthy women using subdermal implants. Norplant-2 was associated with an increased risk of irregular bleeding and a decreased risk of amenorrhea or infrequent bleeding. The leave-one-out analysis and heterogeneity were well distributed among studies for all evaluated outcomes. CONCLUSIONS: Reproductive-aged women in use of subdermal implants experienced a higher rate of acne, weight gain, device removal due to side effects and dissatisfaction compared to those in use of LNG-IUS. TRIAL REGISTRATION: PROSPERO ID: CRD42024516472.