BACKGROUND: Pregnancies conceived through assisted reproductive technology (ART) have a substantially elevated risk of pre-eclampsia, and international guideline classify ART as a high-risk factor warranting low-dose aspirin prophylaxis. However, data on aspirin utilisation and effectiveness in ART pregnancies in sub-Saharan Africa are scare. METHODS: A prospective cohort study was conducted at four private ART centres in Kumasi, Ghana, from August 2024 to February 2025. Women with ongoing In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) pregnancies at ≥ 20 weeks of gestation were consecutively enrolled and categorized by aspirin status (50 exposed and 50 unexposed). Pre-eclampsia was diagnosed according to the 2021 International Society for the Study of Hypertension in Pregnancy criteria. Data were analysed using SPSS version 27 with significance set at p < 0.05. RESULTS: In a cohort of 100 women (mean age of 40.8 years), aspirin use was associated with a lower incidence of pre-eclampsia (10.0% vs. 34.0%; relative risk (RR) 0.29, 95% confidence interval (CI) 0.11-0.76; p = 0.004). The mean gestational age at pre-eclampsia diagnosis was delayed in aspirin users (36.46 ± 1.07 weeks vs. 32.60 ± 4.34 weeks; p = 0.099). Early-onset pre-eclampsia (< 34 weeks) occurred in 0% of aspirin users compared to 42.9% of affected non-users. Aspirin use was significantly associated with fewer preterm deliveries (p=0.009), higher 5-minute appearance, pulse, grimace, activity, respiration (Apgar) scores (p = 0.034), and shorter maternal hospital stays(p=0.020). CONCLUSIONS: Low-dose aspirin significantly reduced the incidence and severity of pre-eclampsia and better perinatal outcomes in this Ghanaian ART cohort. Despite its high efficacy, prophylaxis remains critically underutilized. These findings support incorporating pre-eclampsia risk assessment and aspirin prophylaxis into routine and preconception ART care.