Tuberculosis (TB) is a serious disease of public health concern, mainly in low- and middle-income countries. Most of these countries have challenges in diagnosis and treatment of TB in people with smear-negative pulmonary tuberculosis (SNPTB), which remains a significant public health challenge because of the global burden of the disease. We evaluated the epidemiology and clinical presentation of SNPTB in a cohort of patients with high HIV burden. The study was a cross-sectional study among patients with SNPTB in four major hospitals that care for TB/HIV patients in north-central Nigeria. All patients 18 years and above who were newly diagnosed as SNPTB, or patients with SNPTB who had not taken TB drugs for up to 2 weeks irrespective of their HIV status were recruited. Demographic data (sex, age), smoking status, and medical history (clinical form of TB, symptoms at admission, diagnostic methods, presence of comorbidities, prior TB treatment) were obtained using a semi-structured questionnaire. Detailed clinical examination was also done on all the study subjects. Baseline results of packed cell volume, HIV test and sputum acid fast bacilli done during TB screening were retrieved from the patients’ case notes and recorded. Also, the base line Chest X-ray films taken during TB screening were reviewed and reported by two radiologists blinded to each other’s reports. The Xpert MTB/RIF tests and sputum culture (using LJ medium) were done in a TB reference laboratory. A total of 150 patients with SNPTB were studied. Majority of the patients were female 93 (62%). The median age of the patients was 36.5 years with greater percentage of the patients within the ages of 25-44 years 92 (61.3%). Twenty-two (14.7%) of the patients had previous TB treatment. History of cigarette smoking was obtained in only 7(4.7%) of the patients while 82 (64.1%) were HIV positive. All the patients had a history of cough for over a period of at least three weeks, while, 27 (18%) reported having hemoptysis. About 87 (58%) had fever and 110 (73.7%) had anemia, while weight loss and night sweat were reported in 98(65.3%) and 82 (54.7%) of the patients respectively. Chest x rays were reported as typical of TB in only 24 (16%) of the patients. Of the 150 sputa sample analyzed, 21/150 (14.0%) and 22/150 (14.7%) where Gene Xpert and sputum culture positive respectively. The sensitivity and specificity of Gene Xpert assay were 81.8% (18/22; 95% CI 61.5 to 92.7%) and 97.4% (112/115; 95% CI 92.6 to 99.1%), respectively. The study found cough, fever and anemia to be the commonest presentation in patient with SNPTB in a high HIV burden patient’s population. There is also relatively high culture positivity among the patients. This underscores the need to expand the facilities for culture and confirmation in TB centers across the country.