Objective: To determine the pattern of diseases and factors affecting the outcome of neonates admitted at the Tamale Teaching Hospital Neonatal Intensive Care Unit (TTH NICU) over three months. Methodology: A hospital-based prospective cohort design was used to collect data from participants. A sample size of 399 neonates (participants) admitted into the NICU from 1st March 2021 to 10th June 2021. Data was obtained using KoboCollect, exported into Excel for cleaning, coding and analysed using SPSS version 20. Results: This study screened a total of 450 neonates under 28 days admitted in the NICU of Tamale Teaching Hospital, Ghana, over three months. Fifty-one of them were rejected, and 399 were included in the final analysis. The mean birth weight was 2600 g (±810g), with 33.1% of the neonates having low birth weight. Three hundred and forty-one (341) (85.5%) neonates survived, while 58 (14.5%) died during hospitalisation. The pattern of diseases showed that neonatal sepsis (37.3%, n=149/399), small for gestational age or low birth weight (SGA/LBW) (33.1%, n=132/399), neonatal jaundice (28.1%, n=112/399), prematurity (23.6%, n=94/399), birth asphyxia (13.5%, n=54/399) and congenital anomalies (7.8%, n=31/399) were the most common causes of admissions. All variables which had an association with neonatal mortality (p <0.05) were entered into a binomial logistic model, prematurity (AOR=6.974, 95% CI: 1.766-27.537; p=0.006) was the main predictor of mortality. Conclusion: The common causes of admission and deaths in the TTH NICU during the study were neonatal sepsis, prematurity, birth asphyxia, LBW/SGA and neonatal jaundice. This highlights the need for interventions to address these conditions as we strive to reduce institutional neonatal mortality.