The COVID-19 pandemic has made significant impacts on public health, including human exposure to airborne pathogens. In healthcare facilities, the locations of return air vents in ventilation systems may have important effects on lowering airborne SARS-CoV-2 transmission. This study conducted experiments to examine the influence of different return air vents’ heights (0.7 m, 1.2 m, and 1.6 m) on the particle removal effects in a simulated patient ward. Three different ventilation systems were examined: top celling air supply-side wall return (TAS), underfloor air supply-side wall return (UFAS) and side wall air supply-side wall return (SAS). CFD simulation was applied to further study the effects of return air inlets’ heights (0.3 m, 0.7 m, 1.2 m, 1.6 m, and 2.0 m) and air exchange rates. The technique for order of preference by similarity to ideal solution (TOPSIS) analysis was used to calculate the comprehensive scores of 60 scenarios using a multi-criterion method to obtain the optimal return air inlets’ heights. Results showed that for each additional 0.5 m distance in most working conditions, the inhalation fraction index of medical staff could be reduced by about 5–20%. However, under certain working conditions, even though the distances between the patients and medical personnel were different, the optimal heights of return air vents were constant. For TAS and UFAS, the optimal return air inlets’ height was 1.2 m, while for SAS, the best working condition was 1.6 m air supply and 0.7 m air return. At the optimum return air heights, the particle decay rate per hour of SAS was 75% higher than that of TAS, and the rate of particle decay per hour of SAS was 21% higher than that of UFAS. The location of return air inlets could further affect the operating cost-effectiveness of ventilation systems: the highest operating cost-effectiveness was 8 times higher than the lowest one.