To mitigate the negative impacts of HIV infection on pregnant women and their children, comprehensive services to prevent mother to child transmission are required. We report the outcomes and challenges of a comprehensive service to prevent mother to child transmission of HIV infection implemented from January to December 2007 in a referral hospital and its rollout clinics in rural Swaziland, Southern Africa. We reviewed monthly reports, hospital registers, and field diaries and interviewed 64 service providers. A total of 460 HIV tests were done on first and repeat antenatal care visits. From the test done, 93.7% of the results were collected. About 69.1% of first-time visitors accepted HIV test. The antenatal coverage of pregnant women with nevirapine (NVP)+/-zidovudine (AZT) was 100%. Of 443 antenatal and post-natal care women who underwent CD4 test, 54.4% collected results. About 16.3% of those who collected results were started on antiretroviral treatment. The percentage of postpartum women discharged with unknown HIV status fell by 64.8%. About 91.5% of HIV-positive women received intrapartum antiretroviral prophylaxis of stat dose NVP and AZT + lamivudine with 1-week postpartum tail. From the exposed newborns, 98.8% received NVP stat dose and AZT. A total of 304 HIV exposed infants of age six weeks to 18 months underwent DNA-PCR test. The prevalence of infection among infants where both mother and infant received antiretroviral prophylaxis was 16.1% (n=243). HIV test acceptance rate at first antenatal care visit, proportion of clients collecting CD4 and DNA-PCR test results were low and call for mechanisms for improvement. The proportion of DNA-PCR-positive exposed infants in this study was higher than other reports from Southern Africa. The variation of the findings could be explained by mode of infant feeding, age of testing and mode of delivery. Provision of comprehensive prevention of mother to child transmission services in resource limited setting is possible but challenged by staff shortage, socio-economic and service-related factors.