Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor, has been used for many years as a key component of many ART regimens. Although highly effective and well-tolerated, it has been associated with proximal renal tubulopathy and Fanconi syndrome. The use of TFD has progressively been replaced by tenofovir alafenamide (TAF) which has a mean 91% lower plasma level. Despite much lower drug exposure and favorable changes in renal biomarkers (proteinuria; creatinine clearance), it has been uncertain if the use of TAF results in better renal outcomes. This study was an integrated analysis of 26 phase 2 and phase 3 clinical trials conducted between 2011 and 2017. The studies include 9,322 adults and children with HIV. There was a cumulative exposure of 12,519 person-years to TAF and 5,947 person-years to TDF. Primary renal safety outcomes included incidence of proximal renal tubulopathy and study-drug renal discontinuation events. There were 0 cases of tubulopathy and 3 cases of drug discontinuation in persons receiving TAF compared to 10 cases of tubulopathy in the TDF group and 14 discontinuations. Although overall the number of clinical events were small, both were statistically significant and support the renal safety of TAF compared to TDF.