Branched broomrape [Phelipanche ramosa (L.) Pomel], a parasitic weed with a broad host range, is a quarantine pest in California. Phelipanche ramosa plants can produce thousands of tiny seeds that are easily spread by farm equipment. Best management practices for reducing dispersal risk include physical cleaning and disinfestation of farm equipment, but data on the efficacy of sanitizers on weed seeds are limited. A three-phase study was undertaken during 2022 to 2023 to evaluate quaternary ammonium compound (QAC) sanitizer efficacy on P. ramosa seed germinability. First, several QAC ingredients were evaluated at various concentrations (0 to 2.5 g per 100 ml) and exposure durations (1, 3, and 5 min) to develop initial germination curves. Second, the experiments were conducted with three commercial QAC sanitizers (MG4-Quat [Mg4], Flo-Quat, and Cleaner QT-185) at the recommended dose (1% v/v) and a field-relevant exposure duration (1 min). The final experiments evaluated commercial QAC sanitizer efficacy in the presence of various debris types. The initial experiments showed that alkyl dimethyl benzyl ammonium chloride (ADAC), didecyl dimethyl ammonium bromide (DDAB), and didecyl dimethyl ammonium chloride (DDAC) effectively prevented P. ramosa germination, but the effective dose for a 50% reduction in P. ramosa seed germination ranged from 0.001% (g per 100 ml) at 10 min with DDAC to 0.35% (g per 100 ml) at 1 min with ADAC. While all three QAC sanitizers reduced seed germination 75% to 100% after a 1-min exposure to the recommended dose (1% v/v), this treatment did not affect seed germination in the presence of soil (100 mg ml−1) or fruit/plant tissue (40 mg ml−1). At higher concentrations of Mg4 (8% v/v), P. ramosa seed germination was reduced by 90% to 100%, even in the presence of soil and plant debris. This study demonstrates that while QAC sanitizers can reduce P. ramosa seed germinability, their efficacy is compromised in the presence of debris. Therefore, physical cleaning to reduce debris loads before QAC application is essential for reducing the risk of P. ramosa seed movement among fields on equipment.