OBJECTIVE: Interruptions in care of people with HIV (PWH) on antiretroviral therapy (ART) are associated with adverse outcomes, but most studies have relied on composite outcomes. We investigated whether mortality risk following care interruptions differed from mortality risk after first starting ART. DESIGN: Collaboration of 18 European and North American HIV observational cohort studies of adults with HIV starting ART between 2004-2019. METHODS: Care interruptions were defined as gaps in contact of ≥365 days, with a subsequent return to care (distinct from loss to follow-up), or ≥270 days and ≥545 days in sensitivity analyses. Follow-up time was allocated to no/pre-interruption or post-interruption follow-up groups. We used Cox regression to compare hazards of mortality between care interruption groups, adjusting for time-updated demographic and clinical characteristics and biomarkers upon ART initiation or re-initiation of care. RESULTS: Of 89197 PWH, 83.4% were male and median age at ART start was 39 years (interquartile range [IQR]: 31-48). 8654 PWH (9.7%) had ≥1 care interruption; 10913 episodes of follow-up following a care interruption were included. There were 6104 deaths in 536,334 person-years, a crude mortality rate of 11.4 (95%CI: 11.1-11.7) per 1000 person-years. The adjusted mortality hazard ratio (HR) for the post-interruption group was 1.72 (95%CI: 1.57-1.88) compared with the no/pre-interruption group. Results were robust to sensitivity analyses assuming ≥270-day (HR 1.49, 95%CI: 1.40-1.60) and ≥545-day (HR 1.67, 95%CI: 1.48-1.88) interruptions. CONCLUSIONS: Mortality was higher among PWH reinitiating care following an interruption, compared with when PWH initially start ART, indicating the importance of uninterrupted care.