AbstractObjectivesMacrophages are among the first cells to interact with the dental implant surface and are critical regulators for controlling the immune response toward biomaterials. Macrophages can polarize between two main phenotypes: proinflammatory M1 macrophages and anti‐inflammatory M2 macrophages. This systematic review aims to determine if a differing macrophage inflammatory response exists on hydrophilic sandblasted large grit, acid‐etched (SLActive) surfaces compared to sandblasted large grit, acid‐etched (SLA) titanium or titanium–zirconium surfaces during in vitro studies.Material and MethodsA systematic search of three electronic databases, Medline, DOSS (Dentistry and Oral Sciences Source), and WoS (Web of Science), was performed. Only in vitro studies were included in this systematic review. The electronic search was supplemented with a search of the references. Genetic expression and production of proinflammatory and anti‐inflammatory proteins were assessed. The synthesis of quantitative data was completed by narrative synthesis.ResultsA total of 906 studies were found with the systematic search. Eight studies remained after the application of inclusion and exclusion criteria. Six studies used murine macrophages, while two used human macrophages. Discs were used in six studies, while dental implants were used in the remaining two studies. Genetic expression and cytokine production of proinflammatory cytokines on SLActive surfaces were reduced compared to SLA. Anti‐inflammatory genetic expression and cytokine production was increased on SLActive surfaces. The overall quality of the included studies was low to moderate.ConclusionsSLActive surfaces modulate macrophages to reduce proinflammatory and increase anti‐inflammatory gene expression and cytokine production compared to SLA surfaces. The in vitro nature of the included studies does not replicate the in vivo healing cascade. Further in vivo studies are required to assess the macrophage response toward SLActive implant surfaces compared to SLA surfaces.