ABSTRACT Objective To determine whether ambulatory (outpatient, OP) treatment of severe nausea and vomiting of pregnancy (NVP) is as effective as inpatient (IP) care. Design Non-blinded randomized control trial (RCT) with patient preference arm Setting Multi-center Participants Women less than 20 weeks pregnant with severe NVP and associated ketonuria Methods Women participating in the RCT were randomized via web-based application to either ambulatory or IP treatment. Women declining randomisation entered the patient preference trial (PPT) arm. Protocols, data collection and follow-up were the same for all participants. Main Outcome Measures Primary outcome was reduction in Pregnancy Unique Quantification of Emesis (PUQE) score at 48 hours. Secondary outcomes were duration of treatment; improvement in symptom scores and ketonuria at 48 hours; re-attendances within 7 days of discharge; and comparison of symptoms at 7 days post discharge Results 152/174 eligible women agreed to participate with 77/152 (51%) recruited to the RCT and 79/152 (49%) to the PPT. Patients were initially compared in 4 groups (randomized IP, randomized OP, non-randomized IP and non-randomized OP). Comprehensive cohort analysis of participants in the (RCT) and (PPT) did not demonstrate any differences in patient demographics or baseline clinical characteristics. Pooled analysis of IP versus OP groups showed no difference in reduction in PUQE score at 48 hours (p=0.86). There was no difference in change in eating score (p=0.69), drinking score (p=0.77), wellbeing rating (p=0.64) or reduction in ketonuria (p=0.47) at 48 hours, with no difference in duration of index treatment episode (p=0.83) or re-attendances within 7 days (p=0.52). Conclusions Ambulatory management is an effective alternative to inpatient management of severe NVP. The trial also demonstrated that many women requiring treatment for HG have a strong preferences regarding treatment setting, which needs to be considered by care providers, especially given the psychological impact of HG.