Importance: Consumers have reported skin rash/irritation and hair loss/breakage with Wen by Chaz Dean Sweet Almond Mint Cleansing Conditioner (WCDSAMCC), however epidemiologic, toxicologic and clinical hair loss studies have not provided an explanation. Contact dermatitis has been hypothesized.Objective: To assess the tolerability of six products: WCDSAMCC, three other hair cleansing conditioners, and two controls [salicylic acid shampoo (SAS) and baby shampoo (BS)].Design: Double-blind, randomized, controlled trial.Setting: Single-site study.Population: General population volunteers.Intervention: Standard semi-open patch tests (SOPTs) and duration-escalation repeat open application tests (ROATs) over 5 weeks.Main Outcome Measures: Primary outcome measure was "stopping point" [ROAT total component score ≥6 (maximum 10) or global ≥4 (maximum 5)]. Secondary outcomes included "any reaction" (ROAT component score ≥1) and SOPT ≥ doubtful.Results: Two hundred of 298 volunteers were enrolled. There were no significant differences in the tolerability of WCDSAMCC and any of the other three hair cleansing conditioners as assessed by SOPT or ROAT. WCDSAMCC was significantly better tolerated than SAS ("stopping point", or "any reaction", p values<0.0001) as well as BS (p = 0.01). The frequency of doubtful SOPT reactions was lowest for WCD (2.2%) and highest for SAS (7.1%, p = 0.04).Conclusions: As assessed by both ROAT and SOPTs, WCDSAMCC was similar in tolerability to three other hair cleansing conditioners and significantly better tolerated than both controls (SAS and BS).Summary: This double-blind, randomized, controlled study found that WCDSAMCC was similar in tolerability to three other HCCs and was significantly better tolerated than both SAS and BS. This study provides critical clinical evidence on the comparative lack of cutaneous effects with use of WCDSAMCC.Trial Registration: NCT03483025 ClinicalTrials.gov.