Purpose: Among ocular hypotensive agents, intrinsic sympathomimetic activity (ISA) is unique to carteolol hydrochloride. This study was conducted to evaluate the central nervous system (CNS) and plasma lipid profiles associated with timolol maleate and carteolol hydrochloride in postmenopausal black women with primary open-angle glaucoma (POAG) or ocular hypertension. Methods: One hundred subjects met the inclusion and exclusion criteria for this randomized, double-masked, multicenter, parallel-group study. After completion of informed consent and complete ophthalmic examination, eligible patients entered a washout period, during which no topical ophthalmic medications were used. Blood samples were obtained for hematology and blood chemistry evaluations. Vital signs, ocular symptoms, Symptom Checklist-90-R (SCL-90-R) evaluation, intraocular pressure (IOP) measurements, and slit-lamp examinations were performed before randomization to treatment with either topical carteolol hydrochloride 1.0% or topical timolol maleate 0.5%. Patients received active medications twice daily and were monitored at 4 weeks and 12 weeks. At the conclusion of treatment, vital signs, ocular symptoms, SCL-90-R evaluation, IOP, slit-lamp examinations, and blood samples were obtained. Results: Compared with baseline, high-density lipoprotein (HDL) cholesterol was significantly decreased (worsened) in the timolol group but did not change significantly in the carteolol group. The between-group difference was statistically significant. Total cholesterol to HDL ratio significantly increased (worsened) in the timolol group compared with baseline but did not change in the carteolol group. The difference between groups was statistically significant. No significant differences were observed between groups in SCL-90-R results for either somatization or depression. Conclusions: These results suggest that topical carteolol hydrochloride may have a more favorable blood lipid profile than topical timolol maleate in postmenopausal black women with POAG or ocular hypertension. Carteolol and timolol appear to have similar CNS side effect profiles.