BackgroundOccupational stress is increasing globally and affecting all workplaces and countries’ health professionals. Despite its significant impact on healthcare delivery, limited studies have actually compared the prevalence, causes, effects, and coping strategies of stress among nurses working in hospitals with variation in capacity and function in Ghana. We, therefore, examined and compared the prevalence, causes, effects and coping strategies of occupational stress among nurses working in a secondary care and tertiary hospital in Ghana.MethodsWe conducted a health facility-based cross-sectional study among 248 nurses from two hospitals (Volta Regional Hospital [VRH] and Ho Teaching Hospital [HTH]). The Perceived Stress Scale (PSS) and Weiman Occupational Stress Scale (WOSS) were used to measure the nurses’ stress levels and causes of occupational stress respectively. A self-reported checklist was used to measure both the effects of stress and strategies. Descriptive analyses and t-tests were performed, and statistical significance was measured at the 0.05 level.ResultsThe majority of nurses 77.8% experienced a moderate level of perceived stress. The total individual mean scores of the nurses from the two hospitals (VRH = 3.02 and HTH = 3.09) were 34% and 37% respectively higher than the established WOSS individual average of 2.25. Nursing difficult patients (t=-1.1196, p = 0.037), Unfriendly relationships with superiors, colleagues, and subordinates (t=-2.3333, p = 0.020), working with incompetent staff (t=-1.3129, p = 0.037) were the statistically significant stressors among nurses in the HTH. Whereas, long work hours (t = 2.0841, p = 0.038) and needle-stick injuries (t = 2.6669, p = 0.008) were the statistically significant stressors among nurses from the VRH. Headache (VRH = 73.8% and HTH = 97.9%), Fatigue (VRH = 68.9% and HTH = 83.5%), Frustration VRH = 50.5% and HTH = 68.3%) and Lack of Concentration (VRH = 81.6% and HTH = 80.0%) were most common effects of occupational stress reported.ConclusionThe majority of nurses reported moderate levels of stress, with the two institutions’ stressors differing. Key causes of stress were needle stick injuries, long hours, dealing with challenging patients and strained interpersonal relationships. Common side effects were headaches, exhaustion, irritability, and trouble focusing. To accelerate progress towards achieving the sustainable development goal (SDG) 3.4 of promoting mental health and well-being by 2030, the 2012 Mental Health Act of Ghana and the Occupational Health and Safety Regulations, should fully and effectively be implemented in health facilities across the country.