Objectives: Mammography screening is generally accepted in women aged 50–69, but the balance between benefits and harms remains controversial in other age groups. This study systematically reviews these effects to inform the European Breast Cancer Guidelines. Methods: We searched PubMed, EMBASE and Cochrane Library for randomised clinical trials (RCTs) or systematic reviews of observational studies in the absence of RCTs comparing invitation to mammography screening to no invitation in women at average breast cancer (BC) risk. We extracted data for mortality, BC stage, mastectomy rate, chemotherapy provision, overdiagnosis and false-positive-related adverse effects. We performed a pooled analysis of relative risks, applying an inverse-variance random-effects model for three age groups (<50, 50–69 and 70–74). GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used to assess the certainty of evidence. Results: We identified 10 RCTs including 616,641 women aged 38–75. Mammography reduced BC mortality in women aged 50–69 (relative risk (RR) 0.77, 95%CI (confidence interval) 0.66–0.90, high certainty) and 70–74 (RR 0.77, 95%CI 0.54–1.09, high certainty), with smaller reductions in under 50s (RR 0.88, 95%CI 0.76–1.02, moderate certainty). Mammography reduced stage IIA+ in women 50–69 (RR 0.80, 95%CI 0.64–1.00, very low certainty) but resulted in an overdiagnosis probability of 23% (95%CI 18–27%) and 17% (95%CI 15–20%) in under 50s and 50–69, respectively (moderate certainty). Mammography was associated with 2.9% increased risk of invasive procedures with benign outcomes (low certainty). Conclusions: For women 50–69, high certainty evidence that mammography screening reduces BC mortality risk would support policymakers formulating strong recommendations. In other age groups, where the net balance of effects is less clear, conditional recommendations will be more likely, together with shared decision-making.