PurposeThis randomized, open-label trial was conducted to investigate the optimal duration of bed rest after intrathecal chemotherapy to reduce the incidence of complications without increasing patients’ tolerance to long-term bed rest.MethodsA total of 390 patients receiving intrathecal chemotherapy were randomly assigned 1:1:1 to undergo bed rest for 6, 8, or 10 h after intrathecal chemotherapy. The primary outcome was the rate of complications after intrathecal chemotherapy. The analysis was per protocol.ResultsA total of 359 patients among the 390 patients in our study completed follow-up with 120 patients in the 6-h group, 120 in the 8-h group, and 119 in the 10-h group. The complications among the three groups differed significantly (P = 0.005). The 6-h group had significantly more complications than the 8- (50, 41.7% vs 29, 24.2%, P = 0.004) and 10-h groups (50, 41.7% vs 31, 26.1%, P = 0.011), whereas the difference between the 8- and 10-h groups was not significant (29, 24.2% vs 31, 26.1%, P = 0.737).ConclusionsThe overall results support that the optimal time interval for bed rest in the supine position after intrathecal chemotherapy is 8 h. This trial is registered with the Chinese Clinical Trial Registry (number ChiCTR-IOR-17011671).