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Objective: Nonadherence to receiving hydroxychloroquine (HCQ) is associated with a three‐fold higher risk of lupus‐related hospitalization. Monitoring HCQ blood levels could improve adherence to receiving HCQ and efficacy. Yet, HCQ level monitoring is not routinely done partially due to cost and coverage concerns. To establish HCQ level monitoring cost‐effectiveness, we reported the following: (1) risk of acute care by HCQ blood levels, and (2) cost of HCQ monitoring versus acute care visits. Methods: HCQ blood levels were measured during routine lupus visits. HCQ levels were categorized as follows: (1) subtherapeutic (<750 ng/mL), (2) therapeutic (750–1,200 ng/mL), or (3) supratherapeutic (>1,200 ng/mL). All lupus‐related acute care visits (emergency room visits/hospitalizations) after the index clinic visit until next follow‐up were abstracted. In our primary analysis, we examined associations between HCQ levels and time to first acute care visit in all patients and subgroups with higher rates of acute care. Results: A total of 39 lupus‐related acute care visits were observed in 181 patients. Therapeutic HCQ blood levels were associated with 66% lower rates of acute care. In our cohort, two groups, Black or Hispanic patients and those with public insurance, faced three to four times higher rates of acute care. Levels within 750 to 1,200 ng/mL were associated with 95% lower rates of acute care use in subgroups with higher acute care use. Conclusion: HCQ blood levels within 750 to 1,200 ng/mL are associated with lower rates of acute care in all patients with lupus, including groups with higher rates of acute care. Future clinical trials should establish the causal association between HCQ level monitoring and acute care in patients with lupus. [ABSTRACT FROM AUTHOR]