This study was conducted to assess knowledge and attitude of medication among Nurses in Federal Neuropsychiatric Hospital, Calabar. Three (3) research questions were raised and one hypothesis formulated to direct the study. The descriptive cross-sectional survey design was used to study a total of one hundred and two (102) nurses selected from the study area using the stratified random sampling technique. A well developed and structured questionnaire was used for data collection. The questionnaire was duly validated and its reliability ensured. Data collected were analyzed using descriptive statistics of frequency count, simple percentage, mean, weighted mean, and standard deviation. The study hypothesis was tested using Pearson Product Moment Correlation Coefficient analysis with its significance level set at 0.05. Findings of the study revealed that majority (73.6%) of the nurses used for the study had adequate knowledge of medication error, and majority (72.6%) had positive attitude towards prevention of medication error in the Hospital. Factors that affect safe medication practices among the nurses include: individual negligence, excessive workload, inadequate staff strength, poor working environment, lack of staff development and training, lack of equipment and supplies, non-regular review of patient’s drugs by doctors, and prescription of under dosage drug by doctors. There is a statistically significant and positive relationship between knowledge and attitude of nurses towards prevention of medication error. Based on these findings, it was recommended that government should employ more qualified nurses to increase the strength of nurses in the Hospital and improve the nurse-patient ratio to avoid excessive workload which is a strong and significant contributing factor to medication error among nurses in the Hospital.