The aim of this research is to establish the challenges to health and safety compliance for construction projects in South East Nigeria. This study which is essentially survey based and empirical collected quantitative and qualitative data through questionnaire survey and field observations. The questionnaires were administered to indigenous construction firms and professionals in the construction projects in Abia, Anambra, Imo, Enugu and Ebonyi States of the South East area of Nigeria which are the study population. The tools used for data analysis were Regression using Friedman Q Test Ranking and crosstab. The findings revealed that the challenges to health and safety compliance in South East Nigeria are bribery and corruption, ignorance of the benefits of compliance, lack of health and safety culture, perception of stakeholders, neglect of human rights and moral values, non-commitment of the major construction players, inadequate training of staff and lack of skilled health and safety personnel, non-inclusion of health and safety in contract document and tendering process and inadequate funding. This study concludes that the lack of awareness and understanding of health and safety significantly hinders compliance to health and safety. The study therefore recommends that using enforcement in form of incentives based approach will equally take care of the identified different challenges to Health and Safety Compliance in South East, Nigeria. Furthermore, the health and safety regulations should not be enforced only through inspections and sanctions, rather there should be economic incentives to encourage and motivate self- compliance.