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BackgroundUnderstanding transmission dynamics is useful for tuberculosis (TB) control. We conducted a population-based molecular epidemiological study to understand TB transmission in Ghana.MethodsMycobacterium tuberculosiscomplex (MTBC) isolates obtained from prospectively-sampled pulmonary TB patients between July, 2012 and December, 2015 were confirmed as MTBC using IS6110PCR. MTBC lineages were identified by large sequence polymorphism and single nucleotide polymorphism assays and further characterized using spoligotyping and standard 15-loci MIRU-VNTR typing. We used the n-1 method to estimate recent TB transmission and identified associated risk factors using logistic regression analysis.FindingsOut of 2,309 MTBC isolates, we identified 1,082 (46·9%) single cases with 1,227 (53·1%) isolates belonging to one of 276 clustered cases (clustering range; 2-35). Recent TB transmission rate was estimated to be 41·2%. While we see no significant difference in the recent transmission rates between lineages ofMycobacterium africanum(lineage-5 (31·8%); lineage-6 (24·7%), p=0·118), we found that lineage-4 belonging to theM. tuberculosistransmitted significantly higher (44·9%, pInterpretationsOur findings indicate high recent TB transmission suggesting occurrences of unsuspected outbreaks. The observed reduced transmission rate ofM. africanumsuggests other factor(s) may be responsible for its continuous presence in West Africa.FundingWellcome Trust Intermediate Fellowship Grant 097134/Z/11/Z to Dorothy Yeboah-Manu.