Objectives: To assess the effectiveness of suprapatellar (SP)-nailing versus infrapatellar (IP)-nailing of tibia fractures in anterior knee pain, complications (retropatellar chondropathy, infection, and malalignment) and physical functioning and quality of life. A clinical question-driven and thorough systematic review of current literature is provided. Data source: PubMed and Embase databases were searched for studies published between 2010 and 2020 relating to SP and IP-nailing of tibia fractures. The study is performed in concordance with PRISMA-guidelines. Study selection: Studies eligible for inclusion were randomized controlled trials, prospective and retrospective observational studies reporting on outcomes of interest. Data extraction: Data extraction was performed independently by 2 assessors. Methodological quality and risk of bias was assessed according to the guidelines of the McMaster Critical Appraisal. Data synthesis: Continuous variables are presented as means with SD and dichotomous variables as frequency and percentages. The weighted mean, standardized weighted mean differences, and 95% confidence interval were calculated. A pooled analysis could not be performed because of differences in outcome measures, time-points, and heterogeneity. Results: Fourteen studies with 1447 patients were analyzed. The weighted incidence of anterior knee pain was 29% after SP-nailing and 39% after IP-nailing, without reported significance. There was a significant lower rate of malalignment after the SP-approach (4% vs. 26%) with small absolute differences in all planes. No substantial differences were observed in retropatellar chondropathy, infection, physical functioning, and quality of life. Conclusions: This systematic review does not reveal superiority of either technique in any of the respective outcomes of interest. Definitive choice should depend on the surgeon's experience and available resources. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.