E-cigarette retail surveillance is needed during regulatory changes, like the U.S. increasing minimum legal sales age to 21 (T21) and flavor restrictions (2019 and 2020) and certain state/localities increasing related restrictions. We examined regulatory compliance (eg, minimum-age signage), promotional strategies (eg, health claims), and products at 2 timepoints among vape shops across six U.S. metropolitan statistical areas (MSAs; Atlanta, Boston, Minneapolis, Oklahoma City, San Diego, Seattle). In summer 2018, pairs of trained auditors assessed randomly selected shops (n = ~30/MSA). In fall 2021, audits were conducted among 2018 shops (if open and allowed) and additional randomly selected shops (n = ~20/MSA). Data from 179 shops in 2018 and 119 in 2021 (43 from the 2018 sample) were compared. There were decreases (p < .01) in the proportion of shops with (1) minimum-age signs (90.5% vs. 73.9%), (2) their own e-liquid brand (68.2% vs. 44.5%), onsite vaping (73.2% vs. 46.2%), counter seating (65.2% vs. 34.5%), and e-liquid sampling (90.0% vs. 33.6%), and (3) signs with product/price promotions (89.9% vs. 65.5%), health/cessation claims (29.1% vs. 12.6%), and cartoon imagery (27.4% vs. 11.8%). The proportions selling wet/dry vaporizers (26.4% vs. 39.5%), CBD products (23.3% vs. 71.4%), and pipes/glassware/papers (18.4% vs. 52.9%) increased. In 2021, many sold THC (12.6% e-liquids, 62.2% other products) and kratom (40.3%). With increasing restrictions (eg, on flavors, sampling, and T21), fewer shops sold their own e-liquid brands or accommodated onsite use/sampling, but fewer also posted minimum-age signage. Notably, more offered cannabis-related products. These changes underscore the need for comprehensive surveillance to assess regulatory impact. The past 6 years marked increasing e-cigarette sales restrictions in the United States, yet limited research has examined the implications for tobacco specialty shops selling e-cigarettes. This study found that, from 2018 to 2021, there were significant decreases in the proportion of vape shops with their own e-liquid, onsite vaping, e-liquid sampling, lounge/counter seating, and price promotions, as well as minimum-age signs. There were increases in the proportion selling cannabis-derived products and related paraphernalia. Tobacco control research and regulatory agencies must consider how tobacco specialty stores have evolved alongside legislative changes that impact them and consumers.