Background: Tuberculosis (TB) is one of the leading causes of morbidity and mortality in Pakistan. Assessment of TB treatment outcomes, monitoring and evaluation of its risk factors in Directly Observed Treatment Short Course (DOTS) are among the major indicators of the performance of a national TB control program. Even though Pakistan ranks 5th among the 22 high-TB burden countries, there are no available data in this regard. Methods: Institution-based retrospective study was conducted to determine the treatment outcome of TB patients and investigate associated risk factors at District Head Quarter Hospital Shangla, Khyber-Pakhtunkhwa, Pakistan. Two-year record (January 2011 to December 2012) of TB clinic of the hospital was reviewed. A total of 493 patients' complete information was reviewed in the study period. Results: Of these, 42.19% were smear-positive pulmonary TB (PTB), 35.09% were smear-negative PTB, and 22.72% were extra-PTB (EPTB). The overall prevalence of smear-positive PTB was 42.19% (95% confidence interval [CI]: 37.9-46.2). Records of the treatment outcome showed that 192 (38.94%) were cured, 276 (55.98%) completed treatment, 13 (2.6%) defaulted, 9 (1.8%) died, 1 (0.2%) treatment failure, and 1 (0.2%) had transferred to other facilities. The overall mean treatment success rate of the TB patients was 94.93%. TB age and TB form or baseline smear were significantly associated with unsuccessful treatment outcome. The risk of unsuccessful outcome was significantly lower among TB patients age < 14 years (Adjusted odds ratio [AOR] = 0.118, 95% CI: 0.022-0.644), and PTB (smear positive: AOR = 0.125, 95% CI: 0.023-0.669; Smear negative: AOR = 0.024, 95% CI: 0.003-0.205) compared to their counterpart. Conclusion: The treatment success rate was high and match the World Health Organization criteria. To sustain the effective implementation of DOTS in the area, effective management, and diagnosis should be given for EPTB.