The aim of this prospective study (20 months) was to assess HIV patients' use of Traditional, Complementary and Alternative Medicine (TCAM) and its effect on ARV adherence at three public hospitals in KwaZulu-Natal, South Africa. Seven hundred and thirty-five (29.8% male and 70.2% female) patients who consecutively attended three HIV clinics completed assessments prior to ARV initiation, 519 after 6 months, 557 after 12 and 499 after 20 months on antiretroviral therapy (ART). Results indicate that following initiation of ARV therapy the use of herbal therapies for HIV declined significantly from 36.6% prior to ARV therapy to 8.0% after 6 months, 4.1% after 12 months and 0.6% after 20 months on ARVs. Faith healing methods (including spiritual practices and prayer) declined from 35.8% to 22.1%, 20.8% and 15.5%, respectively. In contrast, the use of micronutrients (vitamins, etc.) significantly increased from 42.6% to 78.2%. The major herbal remedies that were used prior to ART were unnamed traditional medicine, followed by imbiza (Scilla natalensis planch), canova (immune booster), izifozonke (essential vitamins mixed with herbs), African potato (Hypoxis hemerocallidea), stametta (aloe mixed with vitamins and herbs) and ingwe (tonic). Herbal remedies were mainly used for pain relief, as immune booster and for stopping diarrhea. As herbal treatment for HIV was associated with reduced ARV adherence, patient's use of TCAM should be considered in ARV adherence management.