OBJECTIVE To compare the optical coherence tomography (OCT) features of acute central serous chorioretinopathy (CSC) versus neovascular age-related macular degeneration (AMD), and to determine if OCT features can distinguish between these two entities. METHODS A retrospective, observational study of 50 eyes with CSC and 50 eyes with neovascular AMD. Stratus OCT line scans (5 mm) were reviewed for presence of subretinal/intraretinal fluid and retinal pigment epithelium detachment. The height of the fluid and detachments were measured using the OCT manual callipers, and the morphology of the highly reflective line was described. RESULTS Intraretinal fluid (IRF), pigment epithelial detachment (PED), irregularities, thickening and attenuation of the highly reflective line were more often associated with AMD. When present, the PED was significantly greater in AMD than CSC. Patients with CSC were more likely to have subretinal fluid (SRF), and when present, the SRF height was significantly greater in CSC. Patients CSC also had more hypertrophic outer retinal changes on OCT compared with AMD. CONCLUSION Neovascular AMD and acute CSC have distinguishing features on OCT that may help clinicians to differentiate accurately between the two conditions primarily using OCT.