Introduction: Mental health-related problems are on the rise among medical doctors, with many house officers (HOs) have quitted training prematurely owing to work and life-related factors. However, the quality of work-life (QOWL) among Malaysian HOs remains unknown. Hence, we aimed to determine the mean score of QOWL and its predictors among HOs working at two tertiary hospitals. Methods: This is a cross-sectional study conducted at two tertiary hospitals in Selangor, between May and August 2019. A stratified random sampling was employed. The Malay version of work-related quality of life scale (M-WRQLS-2) and the patient health questionnaire (M-PHQ-9) were used for data collection. Statistical analysis was performed using the SPSS version 23.0 (IBM, Chicago, IL). Results: A total of 260 (72.9%) respondents completed the questionnaires. The overall score of QOWL was 3.05 ± 0.48 (95% CI: 2.99, 3.11). Depressed HOs had a significantly lower mean score across all subscales (p < 0.005) except for the stress at work (SAW) subscale. Two predictors were inversely associated with QOWL. These were the M-PHQ-9 score [β= -0.049,95% CI: -0.06, -0.04] and being female [β=-0.129,95% CI: -0.24, -0.02]. Conclusion: HOs who worked at the two hospitals in Selangor perceived their overall QOWL as average. However, being female and having depression were found to be associated with lower QOWL. Therefore, early interventions targeting female HOs and those with depressive symptoms are warranted. Further research and strategies aiming to improve the overall quality of work-life and its dimensions for HOs during housemanship training are vital.