We conducted a retrospective database study to examine the risk of relapse among patients with multiple sclerosis (MS) who were simultaneously prescribed glatiramer acetate (GA) and antihistamine (AH) therapy. Medical and pharmacy claims data were culled from the PharMetrics Patient‐Centric Database from January 1997 to March 2004. GA users were identified and followed until discontinuation or end of health‐plan enrollment. Patients receiving concomitant prescription AH therapy were identified; because over‐the‐counter AH (OTC‐AH) use was not detectable but represented a potential exposure of interest, the presence of allergy‐related medical encounters (i.e., use of allergy medications or visits to allergists or immunologists) was used as a proxy. The outcome of interest was the rate of MS relapse (i.e., hospitalization for MS or an outpatient encounter followed by steroid taper). A recurrent‐event adaptation of Cox proportional hazards regression was used for adjusted relapse risk estimates. A total of 4,334 patients receiving GA therapy were identified and followed for 10 months on average; 537 (12.4%) had concomitant AH use, and 1,015 (23.4%) were potential OTC‐AH recipients. The mean (SD) age of the sample was 42.9 (9.6) years; 78% were female. The overall incidence of relapse was 169.1 events per 1,000 person‐years. Concomitant AH use did not significantly affect relapse risk in recurrent‐event modeling controlling for age, sex, OTC‐AH use, and prior relapse (hazard ratio [HR] = 0.816; 95% confidence interval [CI] = 0.638, 1.043). A second model was specified excluding potential OTC‐AH users; findings for AH were similar (HR = 0.962, 95% CI = 0.675, 1.373). In conclusion, our findings indicate that concomitant use of prescription AHs with GA therapy does not appear to significantly affect the risk of relapse among patients with multiple sclerosis.