Motivated by recent advances in mapping mesoscale eddy tracer mixing in the ocean we evaluate the sensitivity of a coarse-resolution global ocean modelto a spatially variable neutral diffusion coefficient κ _n(x, y, z). We gradually introduce physically motivated models for the horizontal (mixing lengththeory) and vertical (surface mode theory) structure of κ_n along with suppression of mixing by mean flows. Each structural feature influences the ocean's hydrography and circulation to varying extents, with the suppression of mixing by mean flows being the most important factor and the vertical structure being relatively unimportant. When utilizing the full theory (experiment “FULL”) the interhemispheric overturning cell is strengthened by 2 Sv at 26°N (a ∼20% increase), bringing it into better agreement with observations. Zonal mean tracer biases are also reduced in FULL. Neutral diffusion impacts circulation through surface temperature-induced changes in surface buoyancy fluxes and nonlinear equation of state effects. Surface buoyancy forcing anomalies are largest in the Southern Ocean where a decreased neutral diffusivity in FULL leads to surface cooling and enhanced dense-to-light surface water mass transformation, reinforced by reductions in cabbeling and thermobaricity. The increased water mass transformation leads to enhanced midlatitude stratification and interhemispheric overturning. The spatial structure for κ_n in FULL is important as it enhances the interhemispheric cell without degrading the Antarctic bottom water cell, unlike a spatially uniform reduction in κ_n.These results highlight the sensitivity of modeled circulation to κ_n and motivate the use of physics-based models for its structure.