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Abstract Background Understanding the type and causes of errors are necessary for the prevention of occurrence or reoccurrence. Therefore addressing the behavior of health professionals on reporting clinical incidents is crucial to create spontaneous knowledge from mistakes and enhance patient safety. Method A mixed type institution-based cross-sectional study design was conducted from March 1 - 30, 2020 in Dessie comprehensive specialized hospital among 319 and 18 participants for the quantitative and qualitative study, respectively. The professions and participants with their assigned proportions were selected using a simple random sampling technique. For quantitative and qualitative data, semi structured questionnaires and interviewer-guided questions were used to collect data, respectively. Finally, qualitative findings were used to supplement the quantitative result. Result The finding showed that the proportion of clinical incident reporting behavior among health professionals was 12.4%. Having training (AOR=3.6, 95% CI, 1.15-11.45), incident reporting help to minimize errors (AOR=2.8, 95% CI, 1.29-6.02), fear of legal penalty (AOR= 0.3, 95% CI, 0.13-0.82), and lack of feedback (AOR=0.3, 95% CI, 0.11-0.90) were identified as significant factors for clinical incident reporting behavior of the health professionals. Conclusions This study showed that the clinical incident reporting behavior of the health professionals was very low. Therefore health professionals should get training on clinical incident reporting and the hospital should have an incident reporting system and guideline.