RBx 11760, a bi-aryl oxazolidinone, was investigated for antibacterial activity against Gram-positive bacteria. The MIC₉₀s of RBx 11760 and linezolid against Staphylococcus aureus were 2 and 4 mg/liter, against Staphylococcus epidermidis were 0.5 and 2 mg/liter, and against Enterococcus were 1 and 4 mg/liter, respectively. Similarly, against Streptococcus pneumoniae the MIC₉₀s of RBx 11760 and linezolid were 0.5 and 2 mg/liter, respectively. In time-kill studies, RBx 11760, tedizolid, and linezolid exhibited bacteriostatic effect against all tested strains except S. pneumoniae. RBx 11760 showed 2-log₁₀ kill at 4× MIC while tedizolid and linezolid showed 2-log₁₀ and 1.4-log₁₀ kill at 16× MIC, respectively, against methicillin-resistant S. aureus (MRSA) H-29. Against S. pneumoniae 5051, RBx 11760 showed bactericidal activity, with 4.6-log₁₀ kill at 4× MIC compared to 2.42-log₁₀ and 1.95-log₁₀ kill for tedizolid and linezolid, respectively, at 16× MIC. RBx 11760 showed postantibiotic effects (PAE) at 3 h at 4 mg/liter against MRSA H-29, and linezolid showed the same effect at 16 mg/liter. RBx 11760 inhibited biofilm production against methicillin-resistant S. epidermidis (MRSE) ATCC 35984 in a concentration-dependent manner. In a foreign-body model, linezolid and rifampin resulted in no advantage over stasis, while the same dose of RBx 11760 demonstrated a significant killing compared to the initial control against S. aureus (P < 0.05) and MRSE (P < 0.01). The difference in killing was statistically significant for the lower dose of RBx 11760 (P < 0.05) versus the higher dose of linezolid (P > 0.05 [not significant]) in a groin abscess model. In neutropenic mouse thigh infection, RBx 11760 showed stasis at 20 mg/kg of body weight, whereas tedizolid showed the same effect at 40 mg/kg. These data support RBx 11760 as a promising investigational candidate.