Background: Successful active surveillance for infectious disease leads to increased case detection and better management outcomes. Because of that, the National Tuberculosis Programme (NTP), Ghana introduced Symptoms-Based Screening (SBS) Tool for TB case finding. Despite these efforts, Ghana has not achieved the 10% target of TB screening in all out-patient departments attendees as recommended by the NTP. Therefore, this study determined the challenges and limitations of the SBS Tool used for active tuberculosis case finding in Ghana. Methods: This study targeted presumptive TB patients resident in Ho Municipality, Ghana. Presumptive TB patients, recruited from Ho Teaching and Ho Municipal Hospitals, were screened with the SBS tool and presumed TB patients tested for M. tuberculosis using microscopy and positive samples confirmed by geneXpert technique. Also health personnel were interviewed to assess the user-friendliness, challenges and limitations associated with the SBS tool. Chi square association of categorical data was done by STATA version 14.1. P-values <0.05 was considered statistically significant. Results: From both hospitals, 636 presumptive patients and 24 health workers participated in this study. Of the total patients screened, 1.73% had active tuberculosis. Coughing for > 2 weeks (x2=24.8; p<0.05); chest pains (x2=28.3; p<0.01) and night sweat (x2=34.8; p<0.05) associated significantly with M. tuberculosis infection status. The main challenge associated with the SBS tool was its unfriendliness for administration while lack of enough indicators to identify other vulnerable individuals to TB (diabetics, cigarette smokers, alcoholics, immunocompromised and malnourished individuals) limited the sensitivity of the tool. Conclusion: The SBS tool was found not to be sensitive enough to identify infected cases. Inclusion of signs and symptoms of diabetes, immuno-suppression and malnutrition in the current tool and subsequent training of all relevant health personnel on the use of the tool could contribute to increase the sensitivity of the tool.