Comparative pharmacoeconomic analysis of benzathine and procaine penicillin in the treatment of early syphilis in Ahmadu Bello University Teaching Hospital, Zaria, northern Nigeria was carried out retrospectively for prescribed/dispensed antibacterial drugs to outpatients with early syphilis among other infectious diseases, by examining outpatients case notes between 2005 and 2007. Results show that benzathine penicillin cost N 4.31/unit of effectiveness while procaine penicillin injection cost N 18.19/unit of effectiveness in the treatment of early syphilis. Benzathine penicillin injection therefore appears to be more cost effective than procaine penicllin injection. Subjecting the cost and effectiveness to sensitivity analysis did not change this conclusion. Statistical analysis shows that there is a statistically significant difference in the effectiveness (outcome) of benzathine penicillin and procaine penicillin injection, (56.2%) (χ2 = 48.58, P