Purpose: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma. Most relapses occur in the first 2 years after diagnosis. Early response assessment with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) may facilitate early change of treatment, thereby preventing ineffective treatment and unnecessary side effects. We aimed to assess the predictive value of visually-assessed interim 18F-FDG PET on progression-free survival (PFS) or event-free survival (EFS) in DLBCL patients treated with first-line immuno-chemotherapy regimens. Methods: For this systematic review and meta-analysis Pubmed, Embase, and the Cochrane Library were searched until July 11, 2017. Prospective and retrospective studies investigating qualitative interim PET response assessment without treatment adaptation based on the interim PET result were eligible. The primary outcome was two-year PFS or EFS. Prognostic and diagnostic measures were extracted and analysed with pooled hazard ratios and Hierarchical Summary Receiver Operator Characteristic Curves, respectively. Meta-regression was used to study covariate effects. Results: The pooled hazard ratio for 18 studies comprising 2,255 patients was 3.13 (95%CI 2.52–3.89) with a 95% prediction interval of 1.68–5.83. In 19 studies with 2,366 patients, the negative predictive value for progression generally exceeded 80% (64–95), but sensitivity (33–87), specificity (49–94), and positive predictive values (20–74) ranged widely. Conclusions: These findings showed that interim 18F-FDG PET has predictive value in DLBCL patients. However, (subgroup) analyses were limited by lack of information and small sample sizes. Some diagnostic test characteristics were not satisfactory, especially the positive predictive value should be improved, before a successful risk stratified treatment approach can be implemented in clinical practice.