Background X-ray imaging is a common procedure performed on a regular basis for diagnostic purposes all over the world. The use of X-rays is increasing rapidly with the introduction of new radiation-oriented therapeutic practices. Although it carries significant diagnostic benefits, extensive exposure to X-ray imaging has been shown to be associated with multiple dose-dependent health risks. Awareness and knowledge among patients regarding the effects of X-ray imaging, therefore, becomes important. Through this study, we aimed to assess the knowledge and awareness of the hazards of X-ray imaging among different groups of patients visiting two of the public sector tertiary hospitals in Karachi, Pakistan. We also aimed to evaluate the necessary safety measures undertaken during X-ray imaging in these hospitals, and the perception of patients regarding the importance of these measures. Materials and methods A cross-sectional study was conducted in October and November 2018 at two well-known public sector tertiary care hospitals, Dr. Ruth KM Pfau Civil Hospital, Karachi and Jinnah Postgraduate Medical Centre, Karachi. A non-probability convenience sampling technique was adapted to recruit 200 participants for the study. A pretested questionnaire was used to assess the knowledge of radiation among patients and their perception regarding the necessary safety measures required to be undertaken during the X-ray imaging procedure. Data were entered and analyzed using the IBM Statistical Package for the Social Sciences 17.0 (IBM Corp., New York, USA). Frequencies were calculated for individual variables. Chi-square test was employed to measure the relationship between categorical variables. A p-value of <0.05 was considered to be significant. Results Out of 200 participants, 58% knew what radiation was, 42% did not. The relationship between the level of education of patients and the awareness of the term ‘radiation’ was found to be statistically significant (p-value = 0.003). Television was the most common source of information (65.5%). One participant (0.5%) thought that it was possible for X-ray imaging to cause cancer. Similarly, only one participant (0.5%) thought that it could cause decreased fertility, five participants (2.5%) thought it could cause burns, seven (3.5%) thought it could cause cataract, and 20 (10%) were of the view that anemia could be caused. The majority of the participants (80.5%) thought that a lead sheet was important during the X-ray procedure for safety and protection. Most participants (71.5%) said that they were never provided with any such lead sheets. When asked if the participants requested for a lead sheet if not provided, the majority (71%) denied requesting for it. On analyzing, we found that a higher percentage of uneducated participants denied requesting a sheet compared to the educated ones. The relationship between the level of education and the choice of requesting for a lead sheet was found to be statistically...