In Kenya, approximately 3.3% to 4% of infants born annually are exposed to HIV due to lack of PMTCT interventions. Factors associated with mother – to – child HIV transmission as not been adequately investigated in Kenya. The study aim was to investigate factors associated with mother – to – child HIV transmission (MTCT) among HIV exposed infants in Siaya County. A retrospective cohort study design was adopted. Data involving 179 HIV exposed infants and their HIV infected mothers were abstracted from maternal child health medical records and retrospectively followed up for 18 months. Data analysis was carried out using SAS 9.4. Descriptive statistics was used to characterize the demographic, clinical and laboratory variables while Chi –Square test (95 % CI) was used to test for association of factors influencing (determinants) transmission of mother to child HIV infection. Out of 179 HIV exposed infants, 145 were followed up and 25 (17%) were found positive. This study found that factors associated with MTCT were provision of mother’s ARVs at ANC, number of ANC visits, infant prophylaxis, and cotrimoxazale (p <0.001, 95% CI). Immunological factors such as CD 4 count, viral load suppression, and presence of opportunist infections were also associated with MTCT (p<0.001, 95% CI). This study recommends consistent provision of maternal ARVs and infant prophylaxis to that HIV infected pregnant mothers; routine monitoring of CD 4 and viral load of HIV infected expectant and lactating mothers; Future studies on evaluation of pre – conception models for HIV infected women intending to conceive.