Few researchers wanted to determine the factors that are linked to increases in weight during randomized trials of antiretroviral treatment (ART) switch randomized clinical studies. In a pooled analysis of 12 prospective clinical trials, virologically suppressed persons living with human immunodeficiency virus (PWH) were randomized to switch or stay on a stable baseline regimen. The researchers looked at demographic factors’ effects, clinical features, and ART on weight gain (SBR). PWH who were randomly assigned to switch to ART (N=4166) and those who remained on SBR (I=3150) both gained weight. At 48 weeks, those who switched gained more weight (1.6 kg, interquartile range [IQR], –.05 to 4.0 versus 0.4 kg, [IQR], –1.8 to 2.4, P<.0001), with the majority of weight increase occurring in the first 24 weeks after switching. Only younger age and a lower baseline BMI were related with any or greater than 10% weight gain among baseline demographic and clinical factors. Switching from efavirenz (EFV) to rilpivirine (RPV) or elvitegravir/cobicistat, as well as switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide, resulted in a 4.6% weight gain by week 48 (6.4% switch and 2.2% SBR) (TAF). Switching from abacavir to TAF was linked with less weight gain than switching from TDF to TAF, and there was no increased risk of gaining more than 10% of body weight. Moderate weight gain was normal after switching to ART, and it usually plateaued after 48 weeks. After the changeover, participants who switched off of EFV and TDF gained the most weight; baseline ART was a predictor of post-switch weight increase. The biological mechanisms underlying the various weight consequences of switching ART medications and the clinical implications need to be investigated further.