Previous randomized trials have demonstrated that rituximab maintenance (R-maintenance) can prolong time to progressive disease in patients with follicular lymphoma (FL). The phase IIIb MAXIMA study (NCT00430352) was a large prospective evaluation of R-maintenance in a daily care setting. The primary objective was safety. Secondary objectives included progression-free survival, overall survival, time to next lymphoma treatment, and partial response (PR) to complete response/unconfirmed (CR/CRu) conversion rate. Patients (n = 545) with first-line or relapsed FL who responded to 8 cycles of rituximab-based induction received R-maintenance every 2 months for 2 years. At study entry, 380 patients had CR or CRu, and 165 had PR. The median age was 57.0 years. The most common non-hematologic adverse events (AEs, excluding infusion-related reactions) were cough (9.9 % of patients), fatigue (7.5 %), nasopharyngitis (7.1 %), back pain (6.5 %), diarrhea (6.9 %), arthralgia (6.0 %), headache and hypertension (5.2 % each), and pyrexia (5.1 %). The majority of AEs were grade 1 or 2. Grade 3, 4, and 5 infections occurred in 21 (3.9 %), 2 (0.4 %), and 1 (0.2 %) patient, respectively. Fifty-one hematologic AEs occurred in 6.6 % (n = 35) of patients. Grade 3/4 prolonged neutropenia and hypogammaglobulinemia occurred in 13 (2.4 %) and 5 (0.9 %) patients, respectively. All cases of prolonged neutropenia or hypogammaglobulinemia were manageable and resolved. Fast infusion did not alter the safety profile. Efficacy was comparable with results from previous trials. R-maintenance is safe in a daily care setting for patients with first-line or relapsed FL.