Objective Drug-induced hemolytic anemia can occur in patients with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. The practice of G6PD-deficiency screening in the rheumatology field has been inconsistent. This study aimed to determine the utility of screening prior to the initiation of hydroxychloroquine and/or sulfasalazine in rheumatology patients in the ambulatory clinics at Stony Brook University Hospital, New York. Methods We conducted a retrospective chart review of cases of rheumatic diseases that were screened for G6PD deficiency at Stony Brook University Hospital ambulatory clinics. Demographic details and relevant clinical and laboratory data of the patients were collected. The data from similar studies in the literature were searched for and reviewed. Results This study consisted of 228 patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome. Among those patients, 94.7% received hydroxychloroquine, sulfasalazine, or dapsone; 41% (89/228) of patients were screened for G6PD deficiency, and the majority of them were on treatment with hydroxychloroquine. Of those patients, 7.9% (five Caucasians and two African Americans) were found to have G6PD deficiency, and two of the G6PD-deficient patients received hydroxychloroquine. There was no incidence of hemolytic anemia documented in any of the seven patients with G6PD deficiency. We reviewed the literature and found three similar studies of patients receiving hydroxychloroquine with no reported hemolytic anemia from different medical centers in the US, and the frequency of G6PD deficiency reported in these studies was 1.4%, 4.0%, and 4.2%, respectively. Conclusions Our study suggests that the frequency of G6PD deficiency in our rheumatic population is similar to that of the general population, and the risk of hemolytic anemia in G6PD deficiency associated with hydroxychloroquine is extremely rare. Hence, G6PD screening may not be recommended prior to starting treatment with hydroxychloroquine.