In Mbagathi District Hospital’s Comprehensive Care Centre a large number of patients are on treatment with the antiretroviral drug TDF+3TC+EFV which is known to cause Central Nervous System Adverse Drug Reactions, but currently no detailed data exists in Mbagathi District Hospital and in Kenya on the prevalence of such adverse effects following the use of the antiretroviral drug Efavirenz. The documented literature that exists is from other countries and may differ from what is experienced in the hospitals and in Kenya due to genetic and socio demographic factors. This study was carried out to determine the prevalence of reported CNS adverse reactions in adult patients taking Efavirenz based regimens, the number of reported CNS ADRs, the Efavirenz based regimen that had the most CNS ADRs, the CD4 counts in the affected patients and the duration of treatment with Efavirenz when most of the adverse reactions occurred. The study was cross sectional with a sample size of 420 HIV positive patients on Efavirenz based regimens. Analysis of the results indicated that the prevalence of CNS adverse drug reactions was 48.6%. The number of reported reactions was 8 and of these the most reported were vertigo (23.8%), nightmares (13.6%) and drowsiness (9.5%). The Efavirenz based regimen that had the highest number of CNS ADRs was TDF/3TC/EFV (190 cases), AZT/3TC/EFV (8 cases) and D4T/3TC/EFV (6 cases) whereas the CD4 count that had the highest number of reports ranged between 200-299 (54.2%), 100-199 (50.7%) > 399 (48.5%), 300-399 (46.1%) and < 100 (41.8%). The respondents who experienced the CNS ADRs stated that they occurred within the first two weeks, were mild, resolved and the medication use was continued. Multivariate analysis identified the factors associated with occurrence of ADRs during treatment and they included gender, nutritional status, concomitant medical conditions and concurrent use of other medications. Binary logistic regression with removal at p<0.05 retained two factors in the final analysis which were health status and concurrent use of other medications during treatment whereby a patient with a BMI of normal (p= 0.039) was 2.02 times more likely to experience a CNS ADR compared to one with BMI of underweight, xix whereas an overweight patient (p=0.011) was 2.48 times more likely to experience a CNS ADR compared to an underweight patient. Similarly, a patient on other medication(s) during treatment was 1.74 times more likely to experience a CNS ADR compared to one not using any other medication (p=0.012). In conclusion, CNS ADRs were found to be prevalent in adult patients taking Efavirenz based regimens in Mbagathi District Hospital’s CCC. Clinicians should recognize high risk patients and start therapy at the lowest effective dose in susceptible patients and also know the patients drug-drug potential interactions