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Background: Invasive cardiac catheterization (CC) temporarily increases pain, discomfort, and anxiety. Procedural sedation is deployed to mitigate these symptoms, though practice varies. Research evaluating peri-procedural patient-reported outcomes is lacking., Methods and Results: We randomized 175 patients undergoing CC to short interval ([SI] group, <6 min) or long interval ([LI] group, ≥6 min) time intervals between initial intravenous sedation and local anesthetic administration. Outcomes included: (1) total pain medication use, (2) patient-reported and behaviorally assessed pain and (3) patient satisfaction during outpatient CC. Generalized linear mixed effect models were used to evaluate the impact of treatment time interval on total medication utilization, pain, and satisfaction. Among enrollees the mean age was 62 (standard deviation [SD] = 13.4), a majority were male (66%), white (74%), and overweight (mean body mass index = 28.5 [SD = 5.6]). Total pain medication use did not vary between treatment groups (p = 0.257), with no difference in total fentanyl (p = 0.288) or midazolam (p = 0.292). Post-treatment pain levels and nurse-observed pain were not statistically significant between groups (p = 0.324 & p = 0.656, respectively. No significant differences with satisfaction with sedation were found between the groups (p = 0.95) Patient-reported pain, satisfaction and nurse-observed measures of pain did not differ, after adjustment for demographic and procedural factors. Analyses of treatment effect modification revealed that postprocedure self-reported pain levels varied systematically between individuals undergoing percutaneous coronary intervention (PCI) (SI = 2.2 [0.8, 3.6] vs. LI = 0.7 [-0.6, 2.0]) compared with participants not undergoing PCI (SI = 0.4 [-0.8, 1.7] vs. LI = 0.7 [-0.3, 1.6]) (p = 0.043 for interaction)., Conclusion: No consistent treatment differences were found for total medication dose, pain, or satisfaction regardless of timing between sedation and local anesthetic. Treatment moderations were seen for patients undergoing PCI. Further investigation of how procedural and individual factors impact the patient experience during CC is needed., (© 2023 Wiley Periodicals LLC.)