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Importance: High-deductible health plans (HDHPs) have grown rapidly and may adversely affect access to comprehensive cancer care., Objective: To evaluate the association of HDHPs with out-of-pocket medical costs and outpatient physician visits among patients with cancer., Design, Setting, and Participants: Using 2003 to 2017 data from the deidentified Optum Clinformatics Data Mart database from individuals with employer-sponsored health coverage, adults aged 18 to 64 years with cancer who were enrolled in low-deductible (≤$500 annually) health plans during a baseline year were identified. Patients whose employers then mandated a switch to an HDHP (≥$1000 annual deductible) were assigned to the HDHP group, while contemporaneous individuals with cancer at baseline who had no option but to continue enrollment in low-deductible plans were assigned to the control group. The 2 groups were matched on demographic variables (age, sex, race and ethnicity, US Census region, rural vs urban, and neighborhood poverty level), cancer type, morbidity score, number of baseline physician visits by specialty type, baseline out-of-pocket costs, and employer characteristics. These cohorts were followed up for up to 3 years after the baseline year. Data were analyzed from July 2021 to December 2022., Exposures: Employer-mandated HDHP enrollment., Main Outcomes and Measures: Out-of-pocket medical expenditures and outpatient visits to primary care physicians, cancer specialists, and noncancer specialists., Results: After matching, the sample included 45 708 patients with cancer (2703 patients in the HDHP group and 43 005 matched individuals in the control group); mean (SD) age in the HDHP and control groups was 52.9 (9.3) years and 52.9 (2.3) years, respectively, with 58.5% females in both groups. The matching procedure yielded variable weights for each individual in the control group, resulting in a weighted control group sample of 2703 patients. Patients with cancer who were switched to HDHPs experienced an increase in annual out-of-pocket medical expenditures of 68.1% (95% CI, 51.0%-85.3%; absolute increase, $1349.80 [95% CI, $1060.30-$1639.20]) after the switch compared with those who remained in traditional health plans. At follow-up, the number of oncology visits did not differ between the 2 groups (relative difference, 0.1%; 95% CI, -8.4% to 9.4%); however, the HDHP group had 10.8% (95% CI, -15.5% to -5.9%) fewer visits to primary care physicians and 5.9% (95% CI, -11.2% to -0.3%) fewer visits to noncancer specialists., Conclusions and Relevance: Results of this cohort study suggest that after enrollment in HDHPs, patients with cancer experienced substantial increases in out-of-pocket medical costs. The number of visits to oncologists was unchanged during follow-up, but the number of visits to noncancer physicians was lower. These findings suggest that HDHPs are unlikely to unfavorably affect key oncology services but might lead to less comprehensive care of cancer survivors.