The direct anterior approach (DAA) for primary total hip arthroplasty (THA) has recently increased in popularity. Recent evidence has raised concerns about whether use of the DAA is associated with increased rates of superficial and deep infection. The aim of this study was to systematically assess the literature and comparatively evaluate the rate of superficial and deep infection following primary THA using the DAA and non-direct anterior (non-DAA) approaches. This study was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement. Primary outcome measures evaluated were rates of superficial and deep infection in patients undergoing DAA and non-DAA primary THA. A total of 1,872 studies were identified in the original search, of which 15 studies satisfied inclusion criteria. Our analysis evaluated 120,910 primary THAs, including 14,908 DAA and 106,002 non-DAA. The rate of superficial infection was 1.08% for DAA compared with 1.24% for non-DAA (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.79 to 1.30, p = 0.921). The rate of deep infection was 0.73% for DAA compared with 0.51% for non-DAA (OR = 1.03, 95% CI = 0.80 to 1.32, p = 0.831). This study found no difference in the rate of superficial or deep infection after primary THA using the DAA versus other surgical approaches. Our results suggest that comparative infection risk need not be a primary driver in the choice of surgical approach. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.