Background and aims People who inject drugs (PWID) are at risk for adverse outcomes across multiple dimensions. While evidence‐based interventions are available, services are often fragmented and difficult to access. We measured the effectiveness of an integrated care van (ICV) that offered services for PWID. Design, setting and participants This was a cluster‐randomized trial, which took place in Baltimore, MD, USA. Prior to randomization, we used a research van to recruit PWID cohorts from 12 Baltimore neighborhoods (sites), currently served by the city's mobile needle exchange program. Intervention and comparator We randomized sites to receive weekly visits from the ICV (n = 6) or to usual services (n = 6) for 14 months. The ICV offered case management; buprenorphine/naloxone; screening for HIV, hepatitis C virus and sexually transmitted infections; HIV pre‐exposure prophylaxis; and wound care. Measurements The primary outcome was a composite harm mitigation score that captured access to evidence‐based services, risk behaviors and adverse health events (range = 0−15, with higher numbers indicating worse status). We evaluated effectiveness by comparing changes in the composite score at 7 months versus baseline in the two study arms. Findings We enrolled 720 cohort participants across the study sites (60 per site) between June 2018 and August 2019: 38.3% women, 72.6% black and 85.1% urine drug test positive for fentanyl. Over a median of 10.4 months, the ICV provided services to 734 unique clients (who may or may not have been cohort participants) across the six intervention sites, including HIV/hepatitis C virus testing in 577 (78.6%) and buprenorphine/naloxone initiation in 540 (74%). However, only 52 (7.2%) of cohort participants received services on the ICV. The average composite score decreased at 7 months relative to baseline, with no significant difference in the change between ICV and usual services (difference in differences: −0.31; 95% confidence interval: −0.70, 0.08; P = 0.13). Conclusions This cluster‐randomized trial in Baltimore, MD, USA, found no evidence that weekly neighborhood visits from a mobile health van providing injection‐drug‐focused services improved access to services and outcomes among people who injected drugs in the neighborhood, relative to usual services. The van successfully served large numbers of clients but unexpectedly low use of the van by cohort participants limited the ability to detect meaningful differences.