Background: Radiation therapy (RT) is a standard treatment for non-metastatic breast cancer and is associated with acute and late toxicities. Intensity-modulated RT (IMRT) may decrease toxicity and is convenient for patients., Objectives: To assess the efficacy and safety of IMRT in women with early stage breast cancer., Design and Setting: Systematic review study; Multi-institutional centers., Methods: Seven databases were searched. Randomized controlled trials (RCT) comparing IMRT with any "non-IMRT" strategies were included. Primary outcomes were local control and acute toxicity. Cochrane Handbook was use to plan and conduct the review, and PRISMA 2020 was used to report results., Results: Five RCT involving 2,556 women (n = 1,283 IMRT; n = 1,274 control arm) were included. Baseline characteristics were similar between trials and arms. Local relapse-free survival rates were not different (hazard-ratio [HR] 0.62; 95%confidence interval [CI] -0.38 to 1.62; P > 0.05); however, IMRT reduced the overall acute toxicity (RR 0.69, 95%CI 0.58 to 0.82; P < 0.00001) and acute moist desquamation (risk-ratio [RR] 0.71, 95%CI 0.60 to 0.82; P < 0.00001). Lymphedema and pneumonitis rates, and survival outcomes were not affected by IMRT. The 2-year telangiectasia rate was decreased with IMRT (RR 0.66, 95%CI 0.47 to 0.93; P = 0.02); however, edema, pain, pigmentation, or fibrosis remained unaffected. IMRT did not improve cosmesis., Conclusions: IMRT improved acute toxicity and lowered telangiectasia rates, without affecting oncological and aesthetic outcomes., Systematic Review Registration: This review was registered at Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD010420. https://doi.org/10.1002/14651858.CD010420.