In Nigeria, little is known about the profile and treatment outcomes of smear-positive pulmonary TB (SPPTB) patients with persistent smear positivity after 2 months of treatment. A retrospective cohort study was carried out to determine the characteristics and treatment outcomes of patients with persistent smear positivity after 2 months of treatment among adults with SPPTB between 2011 and 2012 in two large health facilities in Nigeria. Findings were compared with SPPTB patients who had a negative smear conversion in the same period. Of 929 eligible patients, 187 (20.1%) had persistent smear positivity after 2 months of treatment. Independent predictors for persistent smear positivity were older age (p<0.001) and care at a public facility (p<0.001). Patients with persistent smear positivity had a higher proportion of unsuccessful treatment outcomes compared with those with a negative smear conversion (21.9% vs 12.4%; p<0.001), mainly due to treatment failure (p<0.001). Across treatment category (new versus previously treated cases), age group and residence category (urban versus rural), rates of unsuccessful outcomes were significantly higher among patients with persistent smear positivity. Treatment outcomes of SPPTB patients with persistent smear positivity were inferior to those who smear converted, with treatment failure being a major problem. This needs to be urgently addressed by the National Tuberculosis Control Programme.