Background Bronchial asthma may mimic different diseases regarding their similar clinical presentations, so accurate assessment is required to exclude other possible diagnosis before confirming the diagnosis of bronchial asthma. The aim of the study was to identify the percentage of patients in whom the diagnosis of current asthma was confirmed or ruled out after clinical, spirometric assessment, and utilizing all the possible investigations. Methods A cohort study of newly diagnosed bronchial asthma in adults aged ≥ 18 years were recruited from chest outpatient clinic and chest department. History taking, clinical examination, chest X-ray, and spirometry were done for all patients, while chest high-resolution computed tomography (HRCT), CT pulmonary angiography, or different endoscopies were done when indicated. Results Two hundred recently clinically diagnosed asthmatic patients were recruited with a mean age of 43.2 and 53.4 years in the asthma group and asthma rule out group, respectively. About 55.5% of the studied patients were ruled out to have bronchial asthma after serial assessments of symptoms and spirometric function. There was increased chest wheeze as a respiratory symptom among asthma patients than the other group (p ˂ 0.001), while hemoptysis was significantly a more presenting symptom among patient group whose asthma diagnosis is ruled out (p = 0.009). About 87.6% of asthma confirmed group showed predominant reversible airway obstructive. The sputum cytology analysis of the bronchial asthma group of patients was 42.7% eosinophilic, 24.7% neutrophilic, and 32.6% mixed cellularity. After consuming all the available investigational tools, the most common diseases found among asthma rule out group were cardiac disorders, chronic obstructive pulmonary disease, psychological disorders, rhinitis, and gastro-esophageal reflux disease with percent of 11.5%, 9%, 8.5%, 8%, and 6%, respectively. Conclusions Utilizing all the available investigational tools in the present study allowed to exclude bronchial asthma and diagnose critical diseases that need specific and urgent therapies as heart diseases, subglottic stenosis, pulmonary hypertension, and interstitial lung diseases. Trial registration ClinicalTrials.gov NCT05776537. Retrospectively registered on 6 March 2023.